Locally Strained 2D Materials: Preparation, Properties, and Applications.

2D materials are promising for strain engineering due to their atomic thickness and exceptional mechanical properties. In particular, non-uniform and localized strain can be induced in 2D materials by generating out-of-plane deformations, resulting in novel phenomena and properties, as witnessed in recent years. Therefore, the locally strained 2D materials are of great value for both fundamental studies and practical applications. This review discusses techniques for introducing local strains to 2D materials, and their feasibility, advantages, and challenges. Then, the unique effects and properties that arise from local strain are explored. The representative applications based on locally strained 2D materials are illustrated, including memristor, single photon emitter, and photodetector. Finally, concluding remarks on the challenges and opportunities in the emerging field of locally strained 2D materials are provided.

Inhibition of NFAT5-Dependent Astrocyte Swelling Alleviates Neuropathic Pain.

Astrocyte swelling is implicated in various neurological disorders. However, whether astrocyte swelling contributes to neuropathic pain remains elusive. This study elucidates the pivotal role of the nuclear factor of activated T-cells 5 (NFAT5) emerges as a master regulator of astrocyte swelling in the spinal dorsal horn (SDH) during neuropathic pain. Despite the ubiquitous expression of NFAT5 protein in SDH cell types, it selectively induces swelling specifically in astrocytes, not in microglia. Mechanistically, NFAT5 directly controls the expression of the water channel aquaporin-4 (AQP4), a key regulator exclusive to astrocytes. Additionally, aurora kinase B (AURKB) orchestrates NFAT5 phosphorylation, enhancing its protein stability and nuclear translocation, thereby regulating AQP4 expression. The findings establish NFAT5 as a crucial regulator for neuropathic pain through the modulation of astrocyte swelling. The AURKB-NFAT5-AQP4 pathway in astrocytes emerges as a potential therapeutic target to combat neuropathic pain.

Growth of 2D Cr2 O3 -CrN Mosaic Heterostructures with Tunable Room-Temperature Ferromagnetism.

2D magnets have generated much attention due to their potential for spintronic devices. Heterostructures of 2D magnets are interesting platforms for exploring physical phenomena and applications. However, the controlled growth of 2D room-temperature ferromagnetic heterostructures is challenging. Here, one-pot chemical vapor deposition growth of stable 2D Cr2 O3 -CrN mosaic heterostructures (MHs) is reported with a controlled ratio of components that possess robust room-temperature ferromagnetism. The 2D MHs consist of Cr2 O3 flakes with embedded CrN subdomains and the CrN:Cr2 O3 ratio can be tuned from 0% to 100% during growth. By changing the CrN:Cr2 O3 ratio, the ferromagnetism of the MHs (e.g., saturation magnetization, coercive field), which originates from the interfacial coupling between Cr2 O3 and CrN, can be controlled. Importantly, the obtained Cr2 O3 -CrN MHs are stable in air at elevated temperatures and have robust ferromagnetism with Curie temperature >400 K. This work presents a facile method for fabricating 2D MHs with tunable magnetism which will benefit high-temperature spintronics.

Resolidified Chalcogen-Assisted Growth of Bilayer Semiconductors with Controlled Stacking Orders.

Bilayer semiconductors have attracted much attention due to their stacking-order-dependent properties. However, as both 3R- and 2H-stacking are energetically stable at high temperatures, most of the high-temperature grown bilayer materials have random 3R- or 2H-stacking orders, leading to non-uniformity in optical and electrical properties. Here, a chemical vapor deposition method is developed to grow bilayer semiconductors with controlled stacking order by modulating the resolidified chalcogen precursors supply kinetics. Taking tungsten disulfide (WS2 ) as an example, pure 3R-stacking (100%) and 2H-stacking dominated (87.6%) bilayer WS2 are grown by using this method and both show high structural and optical quality and good uniformity. Importantly, the bilayer 3R-stacking WS2 shows higher field effect mobility than 2H-stacking samples, due to the difference in stacking order-dependent surface potentials. This method is universal for growing other bilayer semiconductors with controlled stacking orders including molybdenum disulfide and tungsten diselenide, paving the way to exploit stacking-order-dependent properties of these family of emerging bilayer materials.

Combined metabolomics and transcriptomics analysis of rats under neuropathic pain and pain-related depression.

Neuropathic pain often leads to negative emotions, which in turn can enhance the sensation of pain. This study aimed to investigate the molecular mechanisms mediating neuropathic pain and negative emotions. Chronic constriction injury (CCI) rats were used as model animals and behavioral tests were conducted to assess pain and negative emotions. Then, the rat anterior cingulate cortex (ACC) was analyzed using UPLC-MS/MS and subsequently integrated with our previously published transcriptome data. Metabolomics analysis revealed that 68 differentially expressed metabolites (DEMs) were identified, mainly in amino acid metabolites and fatty acyls. Combined with our previously published transcriptome data, we predicted two genes that potentially exhibited associations with these metabolites, respectively Apolipoprotein L domain containing 1 (Apold1) and WAP four-disulfide core domain 1 (Wfdc1). Taken together, our results indicated that peripheral nerve injury contributing to neuropathic pain and pain-related depression may be associated with these metabolites and genes. This research provides new insights into the molecular regulatory mechanism, which could serve as a reference for the treatment of neuropathic pain and pain-related depression.

A Cascade Signal Amplification Strategy for the Ultrasensitive Fluorescence Detection of Cu2+ via λ-Exonuclease-Assisted Target Recycling with Mismatched Catalytic Hairpin Assembly.

Herein, an ultrasensitive DNAzyme-based fluorescence biosensor for detecting Cu2+ was designed using the cascade signal amplification strategy, coupling λ-exonuclease-assisted target recycling and mismatched catalytic hairpin assembly (MCHA). In the designed detection system, the target, Cu2+, can activate the Cu2+-dependent DNAzyme to cause a cleavage reaction, releasing ssDNA (tDNA). Then, tDNA binds to hairpin DNA (H0) with an overhanging 5'-phosphorylated terminus to form dsDNA with a blunt 5'-phosphorylated terminus, which activates the dsDNA to be digested by λ-Exo and releases tDNA along with another ssDNA (iDNA). Subsequently, the iDNA initiates MCHA, which can restore the fluorescence of carboxyfluorescein (FAM) previously quenched by tetramethylrhodamine (TAMRA), resulting in a strong fluorescent signal. Furthermore, MCHA efficiently improves the signal-to-noise ratio of the detection system. More importantly, tDNA recycling can be achieved with the λ-Exo digestion reaction to release more iDNA, efficiently amplifying the fluorescent signal and further improving the sensitivity to Cu2+ with a detection limit of 60 fM. The practical application of the developed biosensor was also demonstrated by detecting Cu2+ in real samples, proving it to be an excellent analytical strategy for the ultrasensitive quantification of heavy metal ions in environmental water sources.

Two Fe(III)/Eu(III) Salophen complex-based optical sensors for determination of organophosphorus pesticide monocrotophos.

Monocrotophos (MP), an organophosphorus pesticide, poses a serious threat to human health, so a rapid and simple technique is needed to detect it. In this study, two novel optical sensors for MP detection were created using the Fe(III) Salophen complex and Eu(III) Salophen complex, respectively. One sensor is an Fe(III) Salophen complex (I-N-Sal), which can bind MP selectively and form a supramolecule, resulting in a strong resonance light scattering (RLS) signal at 300 nm. Under the optimum conditions, the detection limit was 30 nM, the linear range was 0.1-1.1 µM, the correlation coefficient R2 = 0.9919, and the recovery rate range was 97.0-103.1%. Interaction properties between the sensor I-N-Sal and MP and the RLS mechanism were investigated using density functional theory (DFT). And another sensor is based on the Eu(III) Salophen complex and 5-aminofluorescein derivatives. The Eu(III) Salophen complex was immobilized on the surface of amino-silica gel (Sigel-NH2) particles as the solid phase receptor (ESS) of MP and 5-aminofluorescein derivatives as the fluorescent (FL)-labeled receptor (N-5-AF) of MP, which can selectively bind the MP and form a sandwich-type supramolecule. Under the optimum conditions, the detection limit was 0.4 µM, the linear range was 1.3-7.0 µM, the correlation coefficient R2 = 0.9983, and the recovery rate range was 96.6-101.1%. Interaction properties between the sensor and MP were investigated by UV-vis, FT-IR, and XRD. Both sensors were successfully applied to the determination of MP content in tap water and camellia.

Downregulation of nuclear STAT2 protein in the spinal dorsal horn is involved in neuropathic pain following chronic constriction injury of the rat sciatic nerve.

Regulation of gene transcription in the spinal dorsal horn (SDH) plays a critical role in the pathophysiology of neuropathic pain. In this study, we investigated whether the transcription factor STAT2 affects neuropathic pain and evaluated its possible mechanisms. A proteomic analysis showed that the nuclear fraction of STAT2 protein in the SDH was downregulated after chronic constriction injury of the rat sciatic nerve, which was associated with the development of neuropathic pain. Similarly, siRNA-induced downregulation of STAT2 in the SDH of naïve rats also resulted in pain hypersensitivity. Using RNA-sequencing analysis, we showed that reduction of nuclear STAT2 after chronic constriction injury was associated with increased expression of microglial activation markers, including the class II transactivator and major histocompatibility complex class II proteins. In addition, siRNA-induced downregulation of STAT2 promoted microglial activation and pro-inflammatory cytokine expression in the SDH. Taken together, these results showed that chronic constriction injury caused downregulation of nuclear STAT2 in the SDH, which may result in microglial activation and development of neuropathic pain. Our findings indicate that restoration of nuclear expression of STAT2 could be a potential pathway for the treatment of neuropathic pain.

Green synthesis of CQDs for determination of iron and isoniazid in pharmaceutical formulations.

Camphor leaves were used as the precursor for the hydrothermal synthesis of carbon quantum dots. The preparation method is simple and rapid, and the raw material is environmentally friendly and easy to obtain. Without additional modification, the carbon quantum dots were used as fluorescent probes for the sensitive and selective detection of Fe3+ and isoniazid at different excitation wavelengths. For Fe3+, at the excitation wavelength of 320 nm, the ratio of fluorescence intensity of CQD solution after adding Fe3+ to CQD solution without Fe3+ addition, F/F0, and Fe3+ concentration showed a good linear relationship in the range of 2.72 × 10-5 to 1.00 × 10-4 mol L-1 (R2 = 0.9912), and the limit of detection was 8.16 µmol L-1. For isoniazid, at the excitation wavelength of 270 nm, the ratio of fluorescence intensity of CQDs solution with isoniazid to CQDs solution without isoniazid, F/F0, and isoniazid concentration showed good linear relationships in the range of 3.81 × 10-6 to 1.00 × 10-5 mol L-1 (R2 = 0.9941) and 1.00 × 10-5 to 2.10 × 10-4 mol L-1 (R2 = 0.9910) respectively, and the limit of detection was 1.14 µmol L-1. A fluorescence method for the determination of Fe and isoniazid content was proposed. The method has been used to detect iron in iron supplement tablets and isoniazid in isoniazid tablets with satisfactory results.

Botulinum toxin type A counteracts neuropathic pain by countering the increase of GlyT2 expression in the spinal cord of CCI rats.

Botulinum toxin type A (BoNT/A) is a potent toxin, acts by cleaving synaptosome-associated-protein-25 (SNAP-25) to regulate the release of the neural transmitter and shows analgesic effect in neuropathic pain. However, the mechanisms of BoNT/A actions involved in nociceptions remain unclear. Glycine transporter 2 (GlyT2) is an isoform of glycine transporters, which plays an important role in the regulation of glycinergic neurotransmission. Inhibition of GlyTs could decrease pain sensation in neuropathic pain, the role of GlyT2 in the analgesic effect of BoNT/A has not been studied yet. In our present study, we demonstrated that the protein levels of GlyT2 and SNAP-25 were upregulated in the spinal cord after the development of chronic constriction injury (CCI)-induced neuropathic pain. Intraplantar application of BoNT/A (20 U/kg) attenuated mechanical allodynia induced by CCI and downregulated GlyT2 expression in the spinal cord. The application of BoNT/A s also decreased the expression of GlyT2 in pheochromocytoma (PC12) cells. Moreover, intrathecal application of lentivirus-mediated GlyT2 reversed the antinociceptive effect of BoNT/A in CCI rats. These findings indicate that GlyT2 contributes to the antinociceptive effect of BoNT/A and suggest a novel mechanism underlying BoNT/A's antinociception action.

A Novel Electrochemical Sensor Modified with a Computer-Simulative Magnetic Ion-Imprinted Membrane for Identification of Uranyl Ion.

In this paper, a novel ion-imprinted electrochemical sensor modified with magnetic nanomaterial Fe3O4@SiO2 was established for the high sensitivity and selectivity determination of UO22+ in the environment. Density functional theory (DFT) was employed to investigate the interaction between templates and binding ligands to screen out suitable functional binding ligand for the reasonable design of the ion imprinted sensors. The MIIP/MCPE (magnetic ion imprinted membrane/magnetic carbon paste electrode) modified with Fe3O4@SiO2 exhibited a strong response current and high sensitivity toward uranyl ion comparison with the bare carbon paste electrodes. Meanwhile, the MCPE was fabricated simultaneously under the action of strong magnetic adsorption, and the ion imprinted membrane can be adsorbed stably on the electrode surface, handling the problem that the imprinted membrane was easy to fall off during the process of experimental determination and elution. Based on the uranyl ion imprinting network, differential pulse voltammetry (DPV) was adopted for the detection technology to realize the electrochemical reduction of uranyl ions, which improved the selectivity of the sensor. Thereafter, uranyl ions were detected in the linear concentration range of 1.0 × 10-9 mol L-1 to 2.0 × 10-7 mol L-1, with the detection and quantification limit of 1.08 × 10-9 and 3.23 × 10-10 mol L-1, respectively. In addition, the sensor was successfully demonstrated for the determination of uranyl ions in uranium tailings soil samples and water samples with a recovery of 95% to 104%.

Dysregulation of Vesicular Glutamate Transporter VGluT2 via BDNF/TrkB Pathway Contributes to Morphine Tolerance in Mice.

Morphine is widely used in the treatment of moderate to severe pain. Long-term use of morphine leads to various adverse effects, such as tolerance and hyperalgesia. Vesicular glutamate transporter 2 (VGluT2) accumulates glutamate into synaptic vesicles and plays multiple roles in the central nervous system. However, the specific role of VGluT2 in morphine tolerance has not been fully elucidated. Here, we investigated the regulatory role of VGluT2 in morphine tolerance and assessed the potential role of the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) pathway in VGluT2 mediated morphine antinociceptive tolerance in mice. In the present study, we found that VGluT2 is upregulated in the spinal cord after the development of morphine tolerance. Furthermore, inhibition of VGluT2 with its antagonist (Chicago sky blue 6 B, CSB6B) or knockdown of VGluT2 by lentivirus restored the analgesic effect of morphine, suppressed the activation of astrocytes and microglia, and decreased glial-derived pro-inflammatory cytokines. Overexpression of VGluT2 by lentivirus facilitated morphine tolerance and mechanical hyperalgesia. In addition, we found the expression of BDNF is correlated with VGluT2 expression in the spinal cord after chronic morphine administration. Intrathecal injection of the BDNF/TrkB pathway antagonist K252a attenuated the development of morphine tolerance and decreased the expression of VGluT2 in the spinal cord, which suggested the BDNF/TrkB pathway participates in the regulation of VGluT2 in morphine tolerance. This study elucidates the functional capability of VGluT2 in modulating morphine tolerance and identifies a novel mechanism and promising therapeutic target for morphine tolerance.

What Is the Optimal Strategy for Drain Removal After Mastectomy and Axillary Surgery in Breast Cancer Patients? A Multicenter, Three-Arm Randomized Clinical Trial.

INTRODUCTION: The best strategy for drain removal after mastectomy and axillary surgery in breast cancer patients has remained controversial. We conducted a multicenter, three-arm randomized clinical trial to determine the optimal strategy. METHODS: A total of 187 eligible breast cancer patients who underwent mastectomy and axillary surgery were randomized into 10 mL (n = 62), 20 mL (n = 63), and 30 mL (n = 63) groups for drain removal on the first day when the output decreased to a corresponding volume in 24 h. The drain duration, total drain duration, incidence of seroma, quality of life, outpatient visit times, healthcare costs, and postoperative complications were evaluated. RESULTS: The median axillary drain durations and total drain durations were all significantly different between three groups (both P < 0.001). The incidences of seroma were 31.1%, 38.3%, and 52.1%, and the difference between the 30 mL and 10 mL groups was significant (RR = 2.41). The 20 mL group reported significantly better quality of life (QoL) in terms of physical functioning (PF) at the 2-week (30 mL versus 20 mL, HR:-14.18) and 3-week (20 mL versus 10 mL, HR: 11.65) follow-up and role functioning (RF) at the 2-week follow-up (20 mL versus 10 mL, HR: 18.15). No between-group differences were found in G-QoL, outpatient visits, costs, or complications. CONCLUSIONS: The 20 mL group had a moderate drain duration, total drain duration, and incidence of seroma but a significant advantage over the other two groups in terms of PF and RF, with relatively low outpatient costs and comparable postoperative complication rates. These findings could aid in clinical decision-making regarding drain removal timing (http://www.chictr.org.cn/: ChiCTR2000028729).

Risk factors and outcomes of urosepsis in patients with calculous pyonephrosis receiving surgical intervention: a single-center retrospective study.

BACKGROUND: Urosepsis is a catastrophic complication, which can easily develop into septic shock and lead to death if not diagnosed early and effectively treated in time. However, there is a lack of evidence on the risk factors and outcomes in calculous pyonephrosis patients. Therefore, this study was conducted to identify risk factors and outcomes of intra- and postoperative urosepsis in this particular population. METHODS: Clinical data of 287 patients with calculous pyonephrosis were collected. In the univariate and multivariate analysis, all patients were divided into urosepsis group and non-urosepsis group. The diagnosis of urosepsis was mainly on the basis of the criteria of American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM). Patient characteristics and outcomes data were analyzed, and risk factors were assessed by binary logistic regression analysis. RESULTS: Of 287 patients, 41 (14.3%) acquired urosepsis. Univariate analysis showed that white blood cell (WBC > 10*10^9/L) before surgery (P = 0.027), surgery types (P = 0.009), hypotension during surgery (P < 0.001) and urgent surgery (P < 0.001) were associated with intra- and postoperative urosepsis for calculous pyonephrosis patients. In multivariate analysis, hypotension during surgery and urgent surgery were closely related to intra- and postoperative urosepsis. Outcome analysis suggested that patients developing urosepsis had a longer intensive care unit (ICU) stay and postoperative hospital stay and higher mortality. CONCLUSIONS: Hypotension during surgery and urgent surgery were risk factors of intra- and postoperative urosepsis for calculous pyonephrosis patients, which may lead to a prolonged ICU stay, postoperative hospital stay and higher mortality.

[Establishment and differential protein identification of two-dimensional gel electrophoresis for proteomics in the spinal cord of morphine-tolerant rats].

OBJECTIVE: To establish a two-dimensional gel electrophoresis (2-DE) map for comparative proteomic analysis of rat spinal cord with chronic morphine tolerance, and to detect differentially expression proteins that are associated with chronic morphine tolerance.
 Methods: Sixteen male SD rats received the intrathecal catheterization operation and they were randomly divided into a morphine tolerance group (MT group, n=8) and a saline group (NS group, n=8). The lumbar enlargement segments of the MT group and the NS group spinal cord were harvested and proteins were separated by 2-DE. Differential proteome profiles were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The 2-DE maps were visualized after coomassie blue staining and analyzed using PDQuest analysis software. Identification of differential protein spots was conducted by MALDI-TOF-MS, and the Mascot query software was used to search Swiss-Prot database for bioinformatics analysis. Western blotting was used to verify the expression of some differentially expressed proteins.
 Results: A total of 1 000 spots were identified in 2-DE maps of rat spinal cord tissues from the MT group and the NS group, and 36 proteins were significantly differentially expressed in the MT group compared with the NS group. Identification was conducted by MALDI-TOF-MS and Swiss-Prot database through Mascot query software, and a total of 14 proteins were obtained. Among them, 2 protein spots were down-regulated in the MT group compared with that in the NS group, and 12 protein spots were up-regulated in the MT group compared with that in the NS group. Two kinds of proteins (NUDAA, ENOG) were verified by Western blotting and the results were consistent with proteomics data.
 Conclusion: The optimized 2-DE profiles for the proteome of spinal cord tissue in rats with chronic morphine tolerance is established preliminarily, which showed that morphine tolerance can cause changes in the expression of various proteins in the spinal cord.

Quantification of electromyographic activity during sleep: a phasic electromyographic metric.

Recording of electromyographic (EMG) activity is considered essential for defining rapid eye movement (REM) sleep and for quantifying certain types of movements in sleep, such as periodic leg movements in sleep (PLMS). However, routine analyses of EMG activity beyond such purposes is performed rarely and quantified seldom, and normative data are lacking. In this study, the authors examined systematic application of a visual scoring system for short-duration (approximately 100-millisecond) phasic EMG activity recorded from five different muscle groups (submentalis, left/right anterior tibialis, left/right brachioradialis) recorded from two different age groups of normal subjects and a group of patients with Parkinson's disease. Quantification of this activity was labeled as a phasic electromyographic metric (PEM). PEM data were compiled separately by REM and non-REM sleep. Results indicated that PEM is a normal part of REM sleep in all muscle groups, more specifically constituting about 5% (SD = 3.1%) of 2.5-second intervals of REM sleep in the mentalis in healthy young adults. It occurs at higher rates in patients with Parkinson's disease, and its quantification in the legs may be influenced to some degree by the presence of PLMS. PEM may be a useful metric amenable to quantification with digital techniques. It may have particular relevance for the identification of neurodegenerative conditions in which disinhibition of midbrain dopaminergic pathways results in excessive motor discharge during sleep.