Clinical Assessment of Magnetic Resonance Spectroscopy and Diffusion-Weighted Imaging in Diffuse Glioma: Insights Into Histological Grading and IDH Classification.

PURPOSE: To assess the diagnostic utility of clinical magnetic resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI) in distinguishing between histological grading and isocitrate dehydrogenase (IDH) classification in adult diffuse gliomas. METHODS: A retrospective analysis was conducted on 247 patients diagnosed with adult diffuse glioma. Experienced radiologists evaluated DWI and MRS images. The Kruskal-Wallis test examined differences in DWI and MRS-related parameters across histological grades, while the Mann-Whitney U test assessed molecular classification. Receiver Operating Characteristic (ROC) curves evaluated parameter effectiveness. Survival curves, stratified by histological grade and IDH classification, were constructed using the Kaplan-Meier test. RESULTS: The cohort comprised 141 males and 106 females, with ages ranging from 19 to 85 years. The Kruskal-Wallis test revealed significant differences in ADC mean, Cho/NAA, and Cho/Cr concerning glioma histological grade (P < .01). Subsequent application of Dunn's test showed significant differences in ADC mean among each histological grade (P < .01). Notably, Cho/NAA exhibited a marked distinction between grade 2 and grade 3/4 gliomas (P < .01). The Mann-Whitney U test indicated that only ADC mean showed statistical significance for IDH molecular classification (P < .01). ROC curves were constructed to demonstrate the effectiveness of the specified parameters. Survival curves were also delineated to portray survival outcomes categorized by histological grade and IDH classification. Conclusions: Clinical MRS demonstrates efficacy in glioma histological grading but faces challenges in IDH classification. Clinical DWI's ADC mean parameter shows significant distinctions in both histological grade and IDH classification.

Endomorphin-2 analogs with C-terminal esterification display potent antinociceptive effects in the formalin pain test in mice.

Previously, we have investigated three C-terminal esterified endomorphin-2 (EM-2) analogs EM-2-Me, EM-2-Et and EM-2-Bu with methyl, ethyl and tert-butyl ester modifications, respectively. These analogs produced significant antinociception in acute pain at the spinal and supraspinal levels, with reduced tolerance and gastrointestinal side effects. The present study was undertaken to determine the analgesic effects and opioid mechanisms of these three analogs in the formalin pain test. Our results demonstrated that intracerebroventricular (i.c.v.) administration of 0.67-20 nmol EM-2 analogs EM-2-Me, EM-2-Et and EM-2-Bu produced dose-dependent antinociceptive effects in both phase Ⅰ and phase Ⅱ of formalin pain. EM-2-Me and EM-2-Bu displayed more potent antinociception than morphine. Especially, EM-2-Bu exhibited the highest antinociception in phase Ⅱ of formalin pain, with the ED50 value being 2.1 nmol. Naloxone (80 nmol, i.c.v.) completely antagonized the antinociceptive effects of EM-2-Me, EM-2-Et and EM-2-Bu (20 nmol, i.c.v.) in both phase I and phase Ⅱ of formalin pain, suggesting a central opioid mechanism. Nevertheless, the antinociception induced by EM-2-Me might be involved in the release of dynorphin A, which subsequently acted on κ- opioid receptor. EM-2-Bu produced the antinociception probably by the direct activation of both µ- and δ-opioid receptors. EM-2-Me, EM-2-Et and EM-2-Bu also produced significant analgesic effects after peripheral administration, and the central opioid receptors were involved. Furthermore, EM-2-Bu had no influence on the locomotor activity after i.c.v. injection. The present investigation demonstrated that C-terminal esterified modifications of EM-2 will be beneficial for developing novel therapeutics in formalin pain.

Novel endomorphin analogues CEMR-1 and CEMR-2 produce potent and long-lasting antinociception with a favourable side effect profile at the spinal level.

BACKGROUND AND PURPOSE: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent µ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined. EXPERIMENTAL APPROACH: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test. KEY RESULTS: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct µ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit. CONCLUSIONS AND IMPLICATIONS: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects.

Device-Independent Quantum Key Distribution Based on the Mermin-Peres Magic Square Game.

Device-independent quantum key distribution (DIQKD) is information-theoretically secure against adversaries who possess a scalable quantum computer and who have supplied malicious key-establishment systems; however, the DIQKD key rate is currently too low. Consequently, we devise a DIQKD scheme based on the quantum nonlocal Mermin-Peres magic square game: our scheme asymptotically delivers DIQKD against collective attacks, even with noise. Our scheme outperforms DIQKD using the Clauser-Horne-Shimony-Holt game with respect to the number of game rounds, albeit not number of entangled pairs, provided that both state visibility and detection efficiency are high enough.

6-Methoxydihydrosanguinarine exhibits cytotoxicity and sensitizes TRAIL-induced apoptosis of hepatocellular carcinoma cells through ROS-mediated upregulation of DR5.

6-methoxydihydrosanguinarine (6-MS), a natural benzophenanthridine alkaloid extracted from Macleaya cordata (Willd.) R. Br, has shown to trigger apoptotic cell death in cancer cells. However, the exact mechanisms involved have not yet been clarified. The current study reveals the underlying mechanisms of 6-MS-induced cytotoxicity in hepatocellular carcinoma (HCC) cells and investigates whether 6-MS sensitizes TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. 6-MS was shown to suppress cell proliferation and trigger cell cycle arrest, DNA damage, and apoptosis in HCC cells. Mechanisms analysis indicated that 6-MS promoted reactive oxygen species (ROS) generation, JNK activation, and inhibits EGFR/Akt signaling pathway. DNA damage and apoptosis induced by 6-MS were reversed following N-acetyl-l-cysteine (NAC) treatment. The enhancement of PARP cleavage caused by 6-MS was abrogated by pretreatment with JNK inhibitor SP600125. Furthermore, 6-MS enhanced TRAIL-mediated HCC cells apoptosis by upregulating the cell surface receptor DR5 expression. Pretreatment with NAC attenuated 6-MS-upregulated DR5 protein expression and alleviated cotreatment-induced viability reduction, cleavage of caspase-8, caspase-9, and PARP. Overall, our results suggest that 6-MS exerts cytotoxicity by modulating ROS generation, EGFR/Akt signaling, and JNK activation in HCC cells. 6-MS potentiates TRAIL-induced apoptosis through upregulation of DR5 via ROS generation. The combination of 6-MS with TRAIL may be a promising strategy and warrants further investigation.

Conjugated topological cavity-states in one-dimensional photonic systems and bio-sensing applications.

Traditional photonic systems are endowed with brand new properties owing to the addition of topological physics with light. A conjugated topological cavity-states (CTCS) in one-dimensional photonic systems is presented, which has not only robust light transport but also ultra-high performances, such as high quality factor (high-Q) and perfect transmission. This extraordinary CTCS can address the bottleneck of typical topological photonic systems, which can only achieve robust light transport without maintaining high performance. Furthermore, the CTCS is especially suitable for bio-photonic sensing with high resolution requirements. An ultra-sensitivity of 2000 nm/RIU and a high-Q of 109 for detecting the concentration of SARS-CoV-2 S-glycoprotein solution are obtained. Notably, the CTCS not only opens new possibilities for advanced photonics but also paves the way for high performance in topological photonic devices.

Toward a Photonic Demonstration of Device-Independent Quantum Key Distribution.

The security of quantum key distribution (QKD) usually relies on that the users' devices are well characterized according to the security models made in the security proofs. In contrast, device-independent QKD-an entanglement-based protocol-permits the security even without any knowledge of the underlying quantum devices. Despite its beauty in theory, device-independent QKD is elusive to realize with current technologies. Especially in photonic implementations, the requirements for detection efficiency are far beyond the performance of any reported device-independent experiments. In this Letter, we report a proof-of-principle experiment of device-independent QKD based on a photonic setup in the asymptotic limit. On the theoretical side, we enhance the loss tolerance for real device imperfections by combining different approaches, namely, random postselection, noisy preprocessing, and developed numerical methods to estimate the key rate via the von Neumann entropy. On the experimental side, we develop a high-quality polarization-entangled photon source achieving a state-of-the-art (heralded) detection efficiency about 87.5%. Although our experiment does not include random basis switching, the achieved efficiency outperforms previous photonic experiments involving loophole-free Bell tests. Together, we show that the measured quantum correlations are strong enough to ensure a positive key rate under the fiber length up to 220 m. Our photonic platform can generate entangled photons at a high rate and in the telecom wavelength, which is desirable for high-speed generation over long distances. The results present an important step toward a full demonstration of photonic device-independent QKD.

Device-Independent Quantum Key Distribution with Random Postselection.

Device-independent quantum key distribution (QKD) can permit the superior security even with unknown devices. In practice, however, the realization of device-independent QKD is technically challenging because of its low noise tolerance. In the photonic setup, due to the limited detection efficiency, a large amount of the data generates from no-detection events which contain few correlations but contribute high errors. Here, we propose the device-independent QKD protocol with random postselection, where the secret keys are extracted only from the postselected subset of outcomes. This could not open the detection loophole as long as the entropy of the postselected subset is evaluated from the information of the entire set of data, including both detection and no-detection events. This postselection has the advantage to significantly reduce the error events, thus relaxing the threshold of required detection efficiency. In the model of collective attacks, our protocol can tolerate detector efficiency as low as 68.5%, which goes beyond standard security proofs. The results make a concrete step for the implementation of device-independent QKD in practice.

Measurement-Device-Independent Verification of a Quantum Memory.

In this Letter we report an experiment that verifies an atomic-ensemble quantum memory via a measurement-device-independent scheme. A single photon generated via Rydberg blockade in one atomic ensemble is stored in another atomic ensemble via electromagnetically induced transparency. After storage for a long duration, this photon is retrieved and interfered with a second photon to perform a joint Bell-state measurement (BSM). The quantum state for each photon is chosen based on a quantum random number generator, respectively, in each run. By evaluating correlations between the random states and BSM results, we certify that our memory is genuinely entanglement preserving.

Novel Cyclic Endomorphin Analogues with Multiple Modifications and Oligoarginine Vector Exhibit Potent Antinociception with Reduced Opioid-like Side Effects.

Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent µ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.

The spinal anti-allodynic effects of endomorphin analogs with C-terminal hydrazide modification in neuropathic pain model.

The present study was undertaken to further investigate the spinal anti-allodynic effects of endomorphins (EMs) and their C-terminal hydrazide modified analogs EM-1-NHNH2 and EM-2-NHNH2 in the spared nerve injury (SNI) model of neuropathic pain in mice. Our results demonstrated that intrathecal (i.t.) administration of endomorphin-1 (EM-1), endomorphin-2 (EM-2), EM-1-NHNH2 and EM-2-NHNH2 produced potent anti-allodynic effects ipsilaterally in neuropathic pain model. Judging from the area under the curve (AUC) values, these two analogs exhibited higher antinociception than their parent peptides. Moreover, they also displayed significant antinociceptive effects in the contralateral paw administered intrathecally. Interestingly, EM-1 and its analog EM-1-NHNH2 displayed their antinociception probably by µ2-opioid receptor subtype since the µ1-opioid receptor antagonist naloxonazine didn't significantly block the anti-allodynia of EM-1 and EM-1-NHNH2, which implied a same opioid mechanism. However, the anti-allodynia induced by EM-2, but not EM-2-NHNH2 was significantly reduced by both µ1-opioid antagonist, naloxonazine and κ-antagonist, nor-binaltorphamine (nor-BNI), indicating multiple opioid receptors were involved in the anti-allodynic effects of EM-2. Most importantly, EM-1-NHNH2 decreased the antinociceptive tolerance, and EM-2-NHNH2 displayed non-tolerance-forming antinociception. Therefore, C-terminal amide to hydrazide conversion changed the spinal antinociceptive profiles of EMs in neuropathic pain. The present investigation is of great value in the development of novel opioid therapeutics against neuropathic pain.

Remote Blind State Preparation with Weak Coherent Pulses in the Field.

Quantum computing has seen tremendous progress in past years. Due to implementation complexity and cost, the future path of quantum computation is strongly believed to delegate computational tasks to powerful quantum servers on the cloud. Universal blind quantum computing (UBQC) provides the protocol for the secure delegation of arbitrary quantum computations, and it has received significant attention. However, a great challenge in UBQC is how to transmit a quantum state over a long distance securely and reliably. Here, we solve this challenge by proposing a resource-efficient remote blind qubit preparation (RBQP) protocol, with weak coherent pulses for the client to produce, using a compact and low-cost laser. We experimentally verify a key step of RBQP-quantum nondemolition measurement-in the field test over 100 km of fiber. Our experiment uses a quantum teleportation setup in the telecom wavelength and generates 1000 secure qubits with an average fidelity of (86.9±1.5)%, which exceeds the quantum no-cloning fidelity of equatorial qubit states. The results prove the feasibility of UBQC over long distances, and thus serves as a key milestone towards secure cloud quantum computing.

Endomorphin-1 analogs with oligoarginine-conjugation at C-terminus produce potent antinociception with reduced opioid tolerance in paw withdrawal test.

For clinical use, it is essential to develop potent endomorphin (EM) analogs with reduced antinociceptive tolerance. In the present study, the antinociceptive activities and tolerance development of four potent EM-1 analogs with C-terminal oligoarginine-conjugation was evaluated and compared in the radiant heat paw withdrawal test. Following intracerebroventricular (i.c.v.) administration, all analogs 1-4 produced potent and prolonged antinociceptive effects. Notably, analogs 2 and 4 with the introduction of D-Ala in position 2 exhibited relatively higher analgesic potencies than those of analogs 1 and 3 with ß-Pro substitution, consistent with their µ-opioid binding characteristic. In addition, at a dose of 50 µmol/kg, endomorphin-1 (EM-1) failed to produce any significant antinociceptive activity after peripheral administration, whereas analogs 1-4 induced potent antinociceptive effects with an increased duration of action. Herein, our results indicated the development of antinociceptive tolerance to EM-1 and morphine at the supraspinal level on day 7. By contrast, analogs 1-4 decreased the antinociceptive tolerance. Furthermore, subcutaneous (s.c.) administration of morphine at 50 µmol/kg also developed the antinociceptive tolerance, whereas the extent of tolerance developed to analogs 1-4 was largely reduced. Especially, analog 4 exhibited non-tolerance-forming antinociception after peripheral administration. The present investigation gave the evidence that C-terminal conjugation of EM-1 with oligoarginine vector will facilitate the development of novel opioid analgesics with reduced opioid tolerance.

Molecular cloning, characterization and expression of the energy homeostasis-associated gene in piglet.

The energy homeostasis-associated (Enho) gene encodes a secreted protein, adropin, which regulates the expression of hepatic lipogenic genes and adipose tissue peroxisome proliferator-activated receptor γ, a major regulator of lipogenesis. In the present study, the porcine (Sus scrofa) homologue of the Enho gene, which was named pEnho, was amplified by reverse transcriptase polymerase chain reaction (RT-PCR) using oligonucleotide primers derived from in silico sequences. The gene sequence was submitted into the GenBank of NCBI, and the access number is GQ414763. The pEnho encodes a protein of 76 amino acids which shows 75% similarity to Homo sapiens adropin. The expression profile of pEnho in tissues (liver, muscle, anterior jejunum, posterior jejunum, and ileum) was determined by quantitative real-time RT-PCR. pEnho was localized on porcine chromosome 10 and no introns were found. In conclusion, pEnho was cloned and analysed with the aim of increasing knowledge about glucose and lipid metabolism in piglets and helping to promote the health and growth of piglets through adropin regulation.

(4R*,5R*)-Diethyl 2-(4-nitro-phen-yl)-1,3-dioxolane-4,5-dicarboxyl-ate.

In the title compound, C(15)H(17)NO(8), the nitro group is essentially coplanar with the aromatic ring [dihedral angle = 6.4 (3) Å]. The five-membered ring has a twist conformation. In the crystal, C-H⋯O inter-actions link the mol-ecules into a helical chain propagating along [010].

(4R*,5R*)-2-(4-Meth-oxy-phen-yl)-1,3-dioxolane-4,5-dicarboxamide.

In the title compound, C(12)H(14)N(2)O(5), the five-membered 1,3-dioxolane ring has a twisted conformation. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into a two-dimensional network lying parallel to the ab plane. There are also C-H⋯π inter-actions present in the crystal structure.

Adsorption of hydrogen isotopes on micro- and mesoporous adsorbents with orderly structure.

The equilibrium and dynamic adsorption data of H(2) and D(2) on different micro- and mesoporous adsorbents with orderly structure including 3A, 4A, 5A, Y, and 10X zeolites; carbon CMK-3; silica SBA-15; and so forth were collected. Critical effect of the nanodimension of adsorbents on the adsorption behavior of hydrogen and its isotopes is shown. The highest adsorption capacity was observed at pore size 0.7 nm, but equal or even larger isotope difference in the equilibrium adsorption was observed at larger pore sizes, whereas the largest isotope difference in the dynamic adsorption was observed at 0.5 nm. The adsorption rate of D(2) is larger than that of H(2) in microporous adsorbents, but the sequence could be switched over in mesoporous materials. Linear relationship was observed between the adsorption capacity for hydrogen and the specific surface area of adsorbents although the adsorbents are made of different material, which provides a convincing proof of the monolayer mechanism of hydrogen adsorption. The linear plot for microporous adsorbents has a larger slope than that for mesoporous adsorbents, which is attributed to the stronger adsorption potential in micropores.