Activation of N-Methyl-D-aspartate receptor contributed to the ultrasonic modulation of neurons in vitro.

Ultrasound stimulation is increasingly used to investigate brain function and treat brain diseases due to its high level of safety and precise spatiotemporal resolution. Therefore, it is crucial to understand the underlying mechanisms involved in ultrasound brain stimulation. In this study, we investigate the role of NMDA receptors in mediating the effects of ultrasound on primary hippocampal neurons in mice. Our results show that ultrasound alone can activate heterologous NMDA receptor subunits, including NR1A, NR2A, and NR2B, in 293T cells, as well as endogenous NMDA receptors in primary neurons. This activation leads to an influx of calcium and an increase in nuclear c-Fos expression in primary neurons that have not been pre-treated with an NMDA receptor inhibitor. In conclusion, our findings demonstrate that NMDA receptors contribute to neuronal activation by ultrasound stimulation in vitro, providing insight into the molecular mechanisms of ultrasound neuromodulation and a new mediator for the sonogenetics technique.

USP11 plays a critical role in the onset and progression of acute graft-versus-host disease：Novel target for precision therapeutics.

Acute graft-versus-host disease (aGvHD) is considered a result of "cytokine storm." Targeted therapeutic interventions on cytokines via ubiquitination regulatory pathways may provide a potential approach for aGvHD treatment. Ubiquitin-specific peptidase 11 (USP11) has been reported to play key roles in a variety of physiopathological processes by regulating the stability and function of several vital protein molecules. However, its role in aGvHD remains unclear. In this study, we identified USP11 was associated with aGvHD in patients. In the aGvHD mouse model, the colon and liver were more seriously affected in recipient mice who received USP11 wt bone marrow (BM) cells and eased after the donor was treated with a USP11 inhibitor or received USP11 ko BM cells. In mouse models, IL-6 was identified as a major effecter in accelerating aGvHD induced by USP11. In the cell model, IL-6 mRNA transcript was affected by USP11. In addition, USP11 also inhibited IL-6 degradation by affecting IL-6 ubiquitination. Furthermore, the positive correlation between USP11 and IL-6 was confirmed in the GvHD patients' samples. Collectively, all results indicated that USP11 played a critical role in the onset and progression of aGvHD. USP11 might be a potential target for aGvHD treatment.

Risk factors associated with intraoperative shivering during caesarean section: a prospective nested case-control study.

BACKGROUND: To study the incidence and risk factors of shivering in pregnant women during cesarean section. METHODS: We performed a prospective nested case-control study involving parturients scheduled for cesarean sections between July 2018 and May 2021. The overall incidence of intraoperative shivering and its potential risk factors were investigated. The potential risk factors evaluated were pain, anxiety, emergency surgery, transfer from the delivery room, epidural labor analgesia, membrane rupture, labor, and the timing of the surgery. Shivering and body temperature at different time points during the cesarean section were also recorded. The selected seven time points were: entering the operating room, post-anesthesia, post-disinfection, post-delivery, post-oxytocin, post additional hysterotonics, and before leaving the operating room. RESULTS: We analyzed 212 cesarean section parturients. The overall incidence of shivering was 89 (42.0%). Multivariate logistic regression showed that anxiety, emergency delivery, and transfer from the delivery room to the operating room increased the overall shivering incidence (odds ratio = 1.77, 2.90, and 3.83, respectively). The peak shivering incidence occurred after skin disinfection (63, 29.7%), and the lowest body temperature occurred after oxytocin treatment (36.24 ± 0.30 °C). Stratified analysis of surgery origin showed that emergency delivery was a risk factor for shivering (odds ratio = 2.99) in women transferred from the obstetric ward to the operating room. CONCLUSION: Shivering occurred frequently during cesarean sections, with the peak incidence occurring after skin disinfection. Anxiety, emergency delivery, and transfer from the delivery room to the operating room increased the risk of shivering development during cesarean sections. TRIAL REGISTRATION: The study protocol was registered online at China Clinical Registration Center (registration number: ChiCTR-ROC-17010532, Registered on 29 January 2017).

Quantum Nonlocality in Any Forked Tree-Shaped Network.

In the last decade, much attention has been focused on examining the nonlocality of various quantum networks, which are fundamental for long-distance quantum communications. In this paper, we consider the nonlocality of any forked tree-shaped network, where each node, respectively, shares arbitrary number of bipartite sources with other nodes in the next "layer". The Bell-type inequalities for such quantum networks are obtained, which are, respectively, satisfied by all (tn-1)-local correlations and all local correlations, where tn denotes the total number of nodes in the network. The maximal quantum violations of these inequalities and the robustness to noise in these networks are also discussed. Our network can be seen as a generalization of some known quantum networks.

Two-step CVD synthesis of NiTe2-MoS2vertical junctions with improved MoS2transistors performance.

The primary challenge for widespread applications of two-dimensional electronics is to achieve satisfactory electrical contacts due to the difficulties in inevitable physical damages and selectively doping during traditional metal integration process. The two-dimensional (2D) metal-semiconductor junctions have attracted captivated attention for potential applications in future atomically thin electronics as perfect candidates for achieving reliable electrical contacts. Here we demonstrate the van der Waals epitaxial growth of 2D NiTe2-MoS2 metal-semiconductor vertical junctions which the upper NiTe2 selectively nucleate at the edge of underlying MoS2. Optical microscopy (OM), scanning electron microscopy (SEM), atomic force microscopy (AFM), and scanning transmission electron microscope (STEM) studies confirm that NiTe2-MoS2 metal-semiconductor vertical junctions are successfully synthesized. Electrical properties of the NiTe2-contacted MoS2 field-effect transistors (FETs) show higher field-effect mobilities (µFE) than those with deposited Cr/Au contacts. This study demonstrates an effective pathway to improved MoS2 transistors performance with metal-semiconductor junctions.

Two-step chemical vapor deposition synthesis of NiTe2-MoS2 vertical junctions with improved MoS2 transistor performance.

The primary challenge for the widespread application of two-dimensional (2D) electronics is to achieve satisfactory electrical contacts because, during the traditional metal integration process, difficulties arise due to inevitable physical damage and selective doping. Two-dimensional metal-semiconductor junctions have attracted attention for the potential application to achieve reliable electrical contacts in future atomically thin electronics. Here we demonstrate the van der Waals epitaxial growth of 2D NiTe2-MoS2 metal-semiconductor vertical junctions where the upper NiTe2 selectively nucleates at the edge of the underlying MoS2. Optical microscopy (OM), scanning electron microscopy (SEM), atomic force microscopy (AFM), and scanning transmission electron microscope (STEM) studies confirmed that NiTe2-MoS2 metal-semiconductor vertical junctions had been successfully synthesized. The electrical properties of the NiTe2-contacted MoS2 field-effect transistors (FETs) showed higher field-effect mobilities (µ FE) than those with deposited Cr/Au contacts. This study demonstrates an effective pathway to improved MoS2 transistor performance with metal-semiconductor junctions.

Low-Intensity Ultrasound Causes Direct Excitation of Auditory Cortical Neurons.

Cochlear implantation is the first-line treatment for severe and profound hearing loss in children and adults. However, deaf patients with cochlear malformations or with cochlear nerve deficiencies are ineligible for cochlear implants. Meanwhile, the limited spatial selectivity and high risk of invasive craniotomy restrict the wide application of auditory brainstem implants. A noninvasive alternative strategy for safe and effective neuronal stimulation is urgently needed to address this issue. Because of its advantage in neural modulation over electrical stimulation, low-intensity ultrasound (US) is considered a safe modality for eliciting neural activity in the central auditory system. Although the neural modulation ability of low-intensity US has been demonstrated in the human primary somatosensory cortex and primary visual cortex, whether low-intensity US can directly activate auditory cortical neurons is still a topic of debate. To clarify the direct effects on auditory neurons, in the present study, we employed low-intensity US to stimulate auditory cortical neurons in vitro. Our data show that both low-frequency (0.8 MHz) and high-frequency (>27 MHz) US stimulation can elicit the inward current and action potentials in cultured neurons. c-Fos staining results indicate that low-intensity US is efficient for stimulating most neurons. Our study suggests that low-intensity US can excite auditory cortical neurons directly, implying that US-induced neural modulation can be a potential approach for activating the auditory cortex of deaf patients.

A Computable Gaussian Quantum Correlation for Continuous-Variable Systems.

Generally speaking, it is difficult to compute the values of the Gaussian quantum discord and Gaussian geometric discord for Gaussian states, which limits their application. In the present paper, for any (n+m)-mode continuous-variable system, a computable Gaussian quantum correlation M is proposed. For any state ρAB of the system, M(ρAB) depends only on the covariant matrix of ρAB without any measurements performed on a subsystem or any optimization procedures, and thus is easily computed. Furthermore, M has the following attractive properties: (1) M is independent of the mean of states, is symmetric about the subsystems and has no ancilla problem; (2) M is locally Gaussian unitary invariant; (3) for a Gaussian state ρAB, M(ρAB)=0 if and only if ρAB is a product state; and (4) 0≤M((ΦA⊗ΦB)ρAB)≤M(ρAB) holds for any Gaussian state ρAB and any Gaussian channels ΦA and ΦB performed on the subsystem A and B, respectively. Therefore, M is a nice Gaussian correlation which describes the same Gaussian correlation as Gaussian quantum discord and Gaussian geometric discord when restricted on Gaussian states. As an application of M, a noninvasive quantum method for detecting intracellular temperature is proposed.

Steering Witness and Steering Criterion of Gaussian States.

Quantum steering is an important quantum resource, which is intermediate between entanglement and Bell nonlocality. In this paper, we study steering witnesses for Gaussian states in continuous-variable systems. We give a definition of steering witnesses by covariance matrices of Gaussian states, and then obtain a steering criterion by steering witnesses to detect steerability of any (m+n)-mode Gaussian states. In addition, the conditions for two steering witnesses to be comparable and the optimality of steering witnesses are also discussed.

The Evolution of the Minimally Invasive Approach and Conventional Median Sternotomy for Coronary Artery Fistula Correction.

BACKGROUND: Minimally invasive cardiac surgery has become a safe and cosmetic alternative to standard median sternotomy. This retrospective study reviews our results and experience with the minimally invasive approach for congenital coronary artery fistula correction, compared with conventional approach. METHODS: From February 2001 to June 2016, 110 patients with isolated coronary artery fistula (CAF) in our centre underwent correction through minimally invasive approach (MIA) (n=65) or standard median sternotomy (SMS) (n=45). Cardiopulmonary bypass (CPB) was used in 16 patients in the SMS group, and all the other patients underwent the procedure without CPB through a standard median sternotomy or minimally invasive approach. RESULTS: There was no in-hospital mortality and no patients reverted to a median sternotomy in the MIA group. Subxiphoid incision (32 cases) and parasternal incision (28 cases) were the most common approaches used for the procedure. The operative time was 67.82±14.4minutes in MIA group and 107.04±27.91minutes (p=0.0001) in the SMS group. The intubation time was 3.58±2.33hours in the MIA group and 6.1±3.26hours in the SMS group (p=0.0001); the intensive care unit (ICU) stay was 10.04±7.95hours in the MIA group and 19.74±7.81hours in the SMS group (p=0.0001). Three patients (two in MIA Group vs one in SMS Group, p=0.787) were identified with a trivial residual shunt during the procedure, which had disappeared by discharge. CONCLUSIONS: Minimally invasive approach can provide an excellent surgical exposure for CAF ligation in selective patients compared with SMS. It is a safe and cosmetic alternative to conventional treatment and minimised the length of stay.

Accurate Device-Free Tracking Using Inexpensive RFIDs.

Without requiring targets to carry any device, device-free-based tracking is playing an important role in many emerging applications such as smart homes, fitness tracking, intruder detection, etc. While promising, current device-free tracking systems based on inexpensive commercial devices perform well in the training environment, but poorly in other environments because of different multipath reflections. This paper introduces RDTrack, a system that leverages changes in Doppler shifts, which are not sensitive to multipath, to accurately track the target. Moreover, RDTrack identifies particular patterns for fine-grained motions such as turning, walking straightly, etc., which can achieve accurate tracking. For the purpose of achieving a fine-grained device-free tracking system, this paper builds a trajectory estimating model using HMM (Hidden Markov Model) to improve the matching accuracy and reduce the time complexity. We address several challenges including estimating the tag influenced time period, identifying moving path and reducing false positives due to multipath. We implement RDTrack with inexpensive commercial off-the-shelf RFID (Radio Frequency IDentification) hardware and extensively evaluate RDTrack in a lobby, staircase and library. Our results show that RDTrack is effective in tracking the moving target, with a low tracking error of 32 cm. This accuracy is robust for different environments, highlighting RDTrack's ability to enable future essential device-free moving-based interaction with RFID devices.

Nonclassicality by Local Gaussian Unitary Operations for Gaussian States.

A measure of nonclassicality N in terms of local Gaussian unitary operations for bipartite Gaussian states is introduced. N is a faithful quantum correlation measure for Gaussian states as product states have no such correlation and every non product Gaussian state contains it. For any bipartite Gaussian state ρ A B , we always have 0 ≤ N ( ρ A B ) < 1 , where the upper bound 1 is sharp. An explicit formula of N for ( 1 + 1 ) -mode Gaussian states and an estimate of N for ( n + m ) -mode Gaussian states are presented. A criterion of entanglement is established in terms of this correlation. The quantum correlation N is also compared with entanglement, Gaussian discord and Gaussian geometric discord.

Quantum Correlation Based on Uhlmann Fidelity for Gaussian States.

A quantum correlation N F G , A for ( n + m ) -mode continuous-variable systems is introduced in terms of local Gaussian unitary operations performed on Subsystem A based on Uhlmann fidelity F. This quantity is a remedy for the local ancilla problem associated with the geometric measurement-induced correlations; is local Gaussian unitary invariant; is non-increasing under any Gaussian quantum channel performed on Subsystem B;and is an entanglement monotone when restricted to pure Gaussian states in the ( 1 + m ) -mode case. A concrete formula for ( 1 + 1 ) -mode symmetric squeezed thermal states (SSTSs) is presented. We also compare N F G , A with other quantum correlations in scale, such as Gaussian quantum discord and Gaussian geometric discord, for two-mode SSTSs, which reveals that N F G , A has some advantage in detecting quantum correlations of Gaussian states.

Comparison of Intrathecal Dexmedetomidine with Morphine as Adjuvants in Cesarean Sections.

To compare the effects of intrathecal dexmedetomidine and intrathecal morphine as supplements to bupivacaine in cesarean sections under spinal anesthesia. Full-term parturients (n=120) undergoing elective cesarean sections under spinal anesthesia were randomly allocated into three groups: Group B received 10 mg bupivacaine, Group BD received 10 mg bupivacaine plus 5 µg dexmedetomidine, and Group BM received 10 mg bupivacaine plus 100 µg morphine. The onset and regression time of sensory and motor blockade, postoperative analgesia, and side effects were recorded. Group BD showed quicker onset time and a longer sensory and motor blockade than other groups (BD vs. B and BD vs. BM, p<0.05). The mean time of sensory regression to the S1 segment was 253.21±42.79 min in group BD, 192.50±40.62 min in group BM and 188.33±37.62 min in group B (p<0.001). Group BD showed an analgesia duration (time to requirement of first rescue analgesic) (17.59±6.23 h) similar to that of group BM (16.78±5.90 h) but longer than that of group B (3.53±1.68 h) (p<0.001). The incidence of pruritus was significantly higher in group BM compared with groups BD and B (p<0.001). Less shivering was observed in group BD than in groups BM and B (p=0.009). So intrathecal dexmedetomidine (5 µg) prolonged the motor and sensory blockade, provided a similar analgesic effect and reduced pruritus and shivering compared with morphine (100 µg) in cesarean sections.

Intrathecal dexmedetomidine as adjuvant to ropivacaine in hysteroscopic surgery: a prospective, randomized control study.

BACKGROUND: To compare the effects and side effects of intrathecal ropivacaine supplemented with dexmedetomidine and fentanyl in hysteroscopic surgery under spinal anesthesia. METHODS: Female patients (n = 108) undergoing operative hysteroscopic procedures under spinal anesthesia were randomly allocated to the following groups for subarachnoid drug delivery: R (n = 36) received 7.5 mg ropivacaine; RD (n = 36) received 7.5 mg ropivacaine plus 5 µg dexmedetomidine; RF (n = 36) received 7.5 mg ropivacaine plus 15 µg fentanyl. The onset and regression time of sensory and motor blockade, together with the postoperative analgesia and side effects were recorded. RESULTS: There was no significant difference as to sensory and motor onset time between groups. RD had significantly longer sensory and motor blockade time than RF and R. The mean time of sensory regression to the S1 segment was 191.25 ± 40.24 minutes in RD, 149.86 ± 37.46 minutes in RF, and 139.44 ± 38.97 minutes in R (RD vs. R and RD vs. RF, p < 0.001). The regression time of motor blockade to Bromage score 0 was 146.31 ± 40.72 minutes in RD, 80.28 ± 41.18 minutes in RF, and 84.94 ± 26.11 minutes in R (RD vs. R and RD vs. RF, p < 0.001). RD produced similar analgesia effect with RF, (2 hour visual analog scale (VAS) was 0.00 ± 0.00 and 0.31 ± 0.79, respectively) better than the R group (1.35 ± 1.65, p < 0.005). No pruritus occurred in the RD group, while the rate was 36.1% in the RF group. However, the RD group produced milder postsurgical hypotension (RD vs. R and RD vs. RF, p < 0.05). CONCLUSION: Intrathecal dexmedetomidine (5 µg) produced prolonged motor and sensory blockade and less pruritus compared with fentanyl (15 µg) in hysteroscopic surgery.

A novel cytoplasmic tail motif regulates mouse corin expression on the cell surface.

Type II transmembrane serine proteases (TTSPs) are important in many biological processes. Cell surface expression is critical for TTSP activation and function. To date, the mechanism underlying TTSP cell surface expression is poorly understood. Corin is a TTSP and acts as the pro-atrial natriuretic peptide convertase that is essential for sodium homeostasis and normal blood pressure. In this study, we investigated how cytoplasmic tail sequences may regulate corin expression and activation on the cell surface. By site-directed mutagenesis, we made mouse corin proteins with truncations or point-mutations in the cytoplasmic tail. We expressed the mutants in transfected HEK293 cells and analyzed corin cell surface expression and activation by Western blotting and flow cytometry. We found that corin truncation mutants lacking a Lys-Phe-Gln sequence at residues 71-73 had higher levels of cell surface expression and activation compared with that in wild-type corin. When Lys-71, Phe-72 and Gln-73 residues were mutated together, but not individually, in corin with the full-length cytoplasmic tail, increased levels of cell surface expression and zymogen activation were also observed. These results indicate that residues Lys-71, Phe-72 and Gln-73 serve as a novel retention motif in the intracellular pathway to regulate corin cell surface expression and activation.

BMI1 reprogrammes histone acetylation and enhances c-fos pathway via directly binding to Zmym3 in malignant myeloid progression.

The polycomb group BMI1 is proved to be crucial in malignant myeloid progression. However, the underlying mechanism of the action of BMI1 in myeloid malignant progression was not well characterized. In this study, we found that the patients of both myelodysplastic syndromes and chronic myeloid leukaemia with BMI1 overexpression had a higher risk in malignant myeloid progression. In vitro gene transfection studies showed that BMI1 inhibited cell myeloid and erythroid differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) and histone deacetylase inhibitor sodium butyrate respectively. BMI1 also resisted apoptosis induced by arsenic trioxide. Moreover, the transcript levels of Runx1 and Pten were down-regulated in Bmi1-transfected cells in company with histone deacetylation modification. By using chromatin immunoprecipitation (ChIP) collaborated with secondary generation sequencing and verified by ChIP-PCR, we found that BMI1 directly bound to the promoter region of Zmym3, which encodes a component of histone deacetylase-containing complexes. In addition, as one of the downstream target genes of this complex, c-fos was activated with increasing histone acetylation when ZMYM3 was suppressed in the Bmi1-transfected cells. These results suggested that BMI1 may reprogramme the histone acetylation profile in multiple genes through either indirect or direct binding effects which probably contributes to the malignant progression of myeloid progenitor cells.

Pulsatilla saponin A, an active molecule from Pulsatilla chinensis, induces cancer cell death and inhibits tumor growth in mouse xenograft models.

BACKGROUND: Many natural compounds possess antitumor growth activities. Pulsatilla chinensis is an herb used in traditional Chinese medicine to treat infectious diseases. More recently, extracts from P chinensis have been shown to contain antitumor activities. MATERIALS AND METHODS: In this study, we isolated Pulsatilla saponin A as an active compound from P chinensis extracts and tested its anticancer activity in vitro and in vivo. RESULTS: In cell culture, Pulsatilla saponin A significantly inhibited the growth of human hepatocellular carcinoma SMCC-7721 cells and pancreatic BXPC3 and SW1990 cancer cells. Similar inhibitory activities were observed when the compound was tested in mouse xenograft tumor models using human hepatocellular carcinoma Bel-7402 and pancreatic cancer SW1990 cells. In Comet assay and flow cytometric analysis of cell cycle distribution and annexin V expression, DNA damage, G2 arrest, and apoptosis were identified in Pulsatilla saponin A-treated cancer cells. Based on the results of Western blotting, p53 and cyclin B protein levels were higher, whereas Bcl-2 protein levels were lower in Pulsatilla saponin A-treated cancer cells than in vehicle-treated cells. CONCLUSIONS: Pulsatilla saponin A may exert its antitumor effect by inducing DNA damage and causing G2 arrest and apoptosis in cancer cells. Pulsatilla saponin A and its derivatives may be developed as a new class of anticancer agents.

Low-intensity ultrasound activates transmembrane chloride flow through CFTR.

Ultrasound has been demonstrated to activate mechanosensitive channels, which is considered the main mechanism of ultrasound neuromodulation. Currently, all channels that have been shown to be sensitive to ultrasound are cation channels. In addition to cation channels, anion channels also play indispensable roles in neural function. However, there have been no research on ultrasound regulation of anion channels until now. If anion channels can be activated by ultrasound as well, they will inevitably lead to more versatility in ultrasound neuromodulation. Cystic fibrosis transmembrane transduction regulator (CFTR) has been demonstrated to be a mechanically sensitive channel, mediating anionic transmembrane flow. To identify that CFTR is sensitive to ultrasound, CFTR was exogenously expressed in HEK293T cells and was stimulated by low intensity ultrasound. Outward currents in CFTR-expressed HEK293T cells were observed by using whole-cell patch clamp when ultrasound (0.8 MHz, 0.20 MPa) was delivered to these cells. These currents were abolished when the CFTR inhibitor (GlyH101) was applied to the solution or chloride ions was cleared from the solution. Meanwhile, the amplitude of these currents increased when the CFTR agonist (Forskolin) was applied. These results suggest that ultrasound stimuli can activate the CFTR to mediate transmembrane flowing of chloride ions at the single cell level. These findings may expand the application of ultrasound in the neuromodulation field.

Development of a fluorometric and colorimetric dual-mode sensing platform for acid phosphatase assay based on Fe3+ functionalized CuInS2/ZnS quantum dots.

BACKGROUND: The spectral dual-mode response towards analyte has been attracted much attention, benefiting from the higher detection accuracy of such strategy in comparison to single signal readout. However, the currently reported dual-mode sensors for acid phosphatase (ACP) activity are still limited, and most of them more or less exist some deficiencies, such as complicated construction procedure, high-cost, poor biocompatibility, aggregation-caused quenching and limited emission capacity. RESULTS: Herein, we employed Fe3+ functionalized CuInS2/ZnS quantum dots (CIS/ZnS QDs) as nanosensor to develop a novel fluorometric and colorimetric dual-mode assay for ACP activity, combing with ACP-triggered hydrolysis of ascorbic acid 2-phosphate (AAP) into ascorbic acid (AA). The Fe3+ binding to CIS/ZnS QDs can be reduced into Fe2+ during the determination, resulting in the dramatically weakened photoinduced electron transfer (PET) effect and the disappearance of competition absorption. Thus, a highly sensitive ACP assay in the range of 0.22-12.5 U L-1 through fluorescence "turn-on" mode has been achieved with a detection of limit (LOD) of 0.064 U L-1. Meanwhile, the ACP activity can also be quantified by spectrophotometry based on the chromogenic reaction of the formed Fe2+ with 1,10-phenanthroline (Phen). Moreover, the designed nanosensor with good biocompatibility was successfully applied to image and monitor the ACP levels in living cells. SIGNIFICANCE: We believe that the proposed method has remarkable advantages and potential application for ACP assay in terms of the high accuracy, simplicity, low cost, as well as its adequate sensitivity.