Digirseophene A promotes recovery in injured developing cerebellum via AMPK/AKT/GSK3ß pathway-mediated neural stem cell proliferation.

Neural stem cells (NSCs) exhibit a remarkable capacity for self-renewal and have the potential to differentiate into various neural lineage cells, which makes them pivotal in the management of neurological disorders. Harnessing the inherent potential of endogenous NSCs for enhancing nerve repair and regeneration represents an optimal approach to addressing diseases of the nervous system. In this study, we explored the potential of a novel benzophenone derivative named Digirseophene A (DGA), which was isolated from the endophytic fungus Corydalis tomentella. Previous experiments have extensively identified and characterized DGA, revealing its unique properties. Our findings demonstrate the remarkable capability of DGA to stimulate neural stem cell proliferation, both in vitro and in vivo. Furthermore, we established a model of radiation-induced cerebellar injury to assess the effects of DGA on the distribution of different cell subpopulations within the damaged cerebellum, thereby suggesting its beneficial role in cerebellar repair. In addition, our observations on a primary NSCs model revealed that DGA significantly increased cellular oxygen consumption, indicating increased energy and metabolic demands. By utilizing various pathway inhibitors in combination with DGA, we successfully demonstrated its ability to counteract the suppressive impacts of AMPK and GSK3ß inhibitors on NSC proliferation. Collectively, our research results strongly suggest that DGA, as an innovative compound, exerts its role in activating NSCs and promoting injury repair through the regulation of the AMPK/AKT/GSK3ß pathway.

Hydroxypropyl Cellulose-Based Orally Dissolving Film Loaded with Insoluble Dexamethasone for Treatment of Oral Ulcers.

Oral ulcers present as recurrent and spontaneous lesions, often causing intolerable burning pain that significantly disrupts patients' daily lives and compromises their quality of life. In addressing this clinical challenge, oral dissolving films (ODFs) have emerged as promising pharmaceutical formulations for oral ulcer management due to their rapid onset of action, ease of administration, and portability. In this study, ODFs containing the insoluble drug dexamethasone (Dex) were formulated for the treatment of oral ulcers in rabbits using a solvent casting method with ethanol as the solvent. To optimize the composition of the ODFs, a Box-Behnken Design (BBD) experiment was employed to investigate the effects of varying concentrations of hydroxypropyl cellulose (HPC), low-substituted hydroxypropyl cellulose (L-HPC), and plasticizer (glycerol) on key parameters, such as disintegration time, tensile strength, and peel-off efficiency of the films. Subsequently, the film properties of the Dex-loaded ODFs (ODF@Dex) were thoroughly assessed, revealing favorable attributes, including homogeneity, mechanical strength, and solubility. Notably, the use of ethanol as the solvent in the ODF preparation facilitated the homogeneous distribution of insoluble drugs within the film matrix, thereby enhancing their solubility and dissolution rate. Leveraging the potent pharmacological activity of Dex, ODF@Dex was further evaluated for its efficacy in promoting ulcer healing and mitigating the expression of inflammatory factors both in vitro and in vivo. The findings demonstrated that the ODF@Dex exerted significant antiulcer effects by modulating the PI3K/Akt signaling pathway, thus contributing to ulcer resolution. In conclusion, our study underscores the potential of HPC-based ODFs formulated with ethanol as a solvent as a promising platform for delivering insoluble drugs, offering a viable strategy for the clinical management of oral ulcers.

TRAF2 associates with cullin neddylation complex assembly.

Cullin-based RING ligases (CRLs) comprise the largest family of ubiquitin E3 ligases. CRL activity is tightly regulated by cullin neddylation, which has been associated with various diseases. Although inhibitors of CRLs neddylation have been reported, there is a lack of small molecules that can selectively target individual cullins. Here, we identified a natural product, liquidambaric acid (LDA), with relatively selective inhibition properties against cullin (Cul) 2 neddylation, and found that its target, Tumor Necrosis Factor receptor-associated factor 2 (TRAF2) was required for the activity. TRAF2 associates with the Cul2 neddylation complex and regulates the machinery assembly, especially that of E2 (UBC12) and E3 (RBX1) enzymes. In addition, we demonstrated that by intervention of the associations between TRAF2 and the neddylation machinery, LDA disturbed NEDD8 transfer from E1 to E2, therefore blocking Cul2 neddylation. Taken together, we show that TRAF2 plays a positive role in neddylation cascades, and we have identified a small molecule capable of selective modulation of cullin neddylation.

Spatial functional reorganizations can serve as potential biomarkers of post facial palsy synkinesis.

Facial palsy can result in a serious complication known as facial synkinesis, causing both physical and psychological harm to the patients. There is growing evidence that patients with facial synkinesis have brain abnormalities, but the brain mechanisms and underlying imaging biomarkers remain unclear. Here, we employed functional magnetic resonance imaging (fMRI) to investigate brain function in 31 unilateral post facial palsy synkinesis patients and 25 healthy controls during different facial expression movements and at rest. Combining surface-based mass-univariate analysis and multivariate pattern analysis, we identified diffused activation and intrinsic connection patterns in the primary motor cortex and the somatosensory cortex on the patient's affected side. Further, we classified post facial palsy synkinesis patients from healthy subjects with favorable accuracy using the support vector machine based on both task-related and resting-state functional magnetic resonance imaging data. Together, these findings indicate the potential of the identified functional reorganizations to serve as neuroimaging biomarkers for facial synkinesis diagnosis.

Platycodin D Ameliorates Type 2 Diabetes-Induced Myocardial Injury by Activating the AMPK Signaling Pathway.

The current study aimed to assess the effectiveness of pharmacological intervention with Platycodin D (PD), a critically active compound isolated from the roots of Platycodon grandiflorum, in mitigating cardiotoxicity in a murine model of type 2 diabetes-induced cardiac injury and in H9c2 cells in vitro. Following oral administration for 4 weeks, PD (2.5 mg/kg) significantly suppressed the elevation of fasting blood glucose (FBG) levels, improved dyslipidemia, and effectively inhibited the rise of the cardiac injury markers creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT). PD treatment could ameliorate energy metabolism disorders induced by impaired glucose uptake by activating AMPK protein expression in the DCM mouse model, thereby promoting the GLUT4 transporter and further activating autophagy-related proteins. Furthermore, in vitro experiments demonstrated that PD exerted a concentration-dependent increase in cell viability while also inhibiting palmitic acid and glucose (HG-PA)-stimulated H9c2 cytotoxicity and activating AMPK protein expression. Notably, the AMPK activator AICAR (1 mM) was observed to upregulate the expression of AMPK in H9c2 cells after high-glucose and -fat exposure. Meanwhile, we used AMPK inhibitor Compound C (20 µM) to investigate the effect of PD activation of AMPK on cells. In addition, the molecular docking approach was employed to dock PD with AMPK, revealing a binding energy of -8.2 kcal/mol and indicating a tight interaction between the components and the target. PD could reduce the expression of autophagy-related protein p62, reduce the accumulation of autophagy products, promote the flow of autophagy, and improve myocardial cell injury. In conclusion, it has been demonstrated that PD effectively inhibits cardiac injury-induced type 2 diabetes in mice and enhances energy metabolism in HG-PA-stimulated H9c2 cells by activating the AMPK signaling pathway. These findings collectively unveil the potential cardioprotective effects of PD via modulation of the AMPK signaling pathway.

EZH2: The roles in targeted therapy and mechanisms of resistance in breast cancer.

Drug resistance presents a formidable challenge in the realm of breast cancer therapy. Accumulating evidence suggests that enhancer of zeste homolog 2 (EZH2), a component of the polycomb repressive complex 2 (PRC2), may serve as a key regulator in controlling drug resistance. EZH2 overexpression has been observed in breast cancer and many other malignancies, showing a strong correlation with poor outcomes. This review aims to summarize the mechanisms by which EZH2 regulates drug resistance, with a specific focus on breast cancer, in order to provide a comprehensive understanding of the underlying molecular processes. Additionally, we will discuss the current strategies and outcomes of targeting EZH2 using both single agents and combination therapies, with the goal of offering improved guidance for the clinical treatment of breast cancer patients who have developed drug resistance.

Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer.

Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894-0.4706, p < 0.0001) and enhanced infiltration of adaptive immune cells. Biomolecular analysis showed that high TLS-score was strongly associated with more infiltration of immune cells and increased activation of immune-related pathways. TLS+ tumors in pre-treatment specimens were associated with a higher proportion of good respond (62.5% vs. 29.8%, p < 0.0002) and pathological complete remission (pCR) (40.0% vs. 11.1%, p < 0.0001), and significantly increased RFS (HR 0.3574 95%CI 0.1489-0.8578 p = 0.0213) compared with TLS- tumors in the neoTx cohort, which was confirmed in GSE119409 and GSE150082. Further studies showed that neoTx significantly reduced TLS density and maturity, and abolished the prognostic value of TLS. Our study illustrates that TLS may have a key role in mediating the T-cell-inflamed tumor microenvironment, which also provides a new direction for neoTx, especially neoadjuvant immunotherapy, in LRAC patients.

Colorectal cancer cells secreting DKK4 transform fibroblasts to promote tumour metastasis.

Wnt/ß-catenin signalling is aberrantly activated in most colorectal cancer (CRC) and is one key driver involved in the initiation and progression of CRC. However, mutations of APC gene in CRC patients retain certain activity of APC protein with decreased ß-catenin signalling and DKK4 expression significantly upregulates and represses Wnt/ß-catenin signalling in human CRC tissues, suggesting that a precisely modulated activation of the Wnt/ß-catenin pathway is essential for CRC formation and progression. The underlying reasons why a specifically reduced degree, not a fully activating degree, of ß-catenin signalling in CRC are unclear. Here, we showed that a soluble extracellular inhibitor of Wnt/ß-catenin signalling, DKK4, is an independent factor for poor outcomes in CRC patients. DKK4 secreted from CRC cells inactivates ß-catenin in fibroblasts to induce the formation of stress fibre-containing fibroblasts and myofibroblasts in culture conditions and in mouse CRC xenograft tissues, resulting in restricted expansion in tumour masses at primary sites and enhanced CRC metastasis in mouse models. Reduced ß-catenin activity by a chemical inhibitor MSAB promoted the CRC metastasis. Our findings demonstrate why reduced ß-catenin activity is needed for CRC progression and provide a mechanism by which interactions between CRC cells and stromal cells affect disease promotion.

Autoimmune nodopathy with anti-contactin 1 antibody characterized by cerebellar dysarthria: a case report and literature review.

Background: Autoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria. Methods: A 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed. Results: The results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative. Conclusion: Apart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.

Combined Photothermal Therapy and Cancer Immunotherapy by Immunogenic Hollow Mesoporous Silicon-Shelled Gold Nanorods.

Hyperthermia can be integrated with tumor-killing chemotherapy, radiotherapy and immunotherapy to give rise to an anti-tumor response. To this end, a nano-delivery system is built, which can connect hyperthermia and immunotherapy. On this basis, the impact of such a combination on the immune function of dendritic cells (DCs) is explored. The core of this system is the photothermal material gold nanorod (GNR), and its surface is covered with a silica shell. Additionally, it also forms a hollow mesoporous structure using the thermal etching approach, followed by modification of targeted molecule folic acid (FA) on its surface, and eventually forms a hollow mesoporous silica gold nanorod (GNR@void@mSiO2) modified by FA. GNR@void@mSiO2-PEG-FA (GVS-FA) performs well in photothermal properties, drug carriage and release and tumor targeting performance. Furthermore, the thermotherapy of tumor cells through in vitro NIR irradiation can directly kill tumor cells by inhibiting proliferation and inducing apoptosis. GVS-FA loaded with imiquimod (R837) can be used as a adjuvant to enhance the immune function of DCs through hyperthermia.

A transferrin receptor targeting dual-modal MR/NIR fluorescent imaging probe for glioblastoma diagnosis.

The prognosis of glioblastoma (GBM) remains challenging, primarily due to the lack of a precise, effective imaging technique for comprehensively characterization. Addressing GBM diagnostic challenges, our study introduces an innovative dual-modal imaging that merges near-infrared (NIR) fluorescent imaging with magnetic resonance imaging (MRI). This method employs superparamagnetic iron oxide nanoparticles coated with NIR fluorescent dyes, specifically Cyanine 7, and targeted peptides. This synthetic probe facilitates MRI functionality through superparamagnetic iron oxide nanoparticles, provides NIR imaging capability via Cyanine 7 and enhances tumor targeting trough peptide interactions, offering a comprehensive diagnostic tool for GBM. Notably, the probe traverses the blood-brain barrier, targeting GBM in vivo via peptides, producing clear and discernible images in both modalities. Cytotoxicity and histopathology assessments confirm the probe's favorable safety profile. These findings suggest that the dual-modal MR\NIR fluorescent imaging probe could revolutionize GBM prognosis and survival rates, which can also be extended to other tumors type.

fMRI, LFP, and anatomical evidence for hierarchical nociceptive routing pathway between somatosensory and insular cortices.

The directional organization of multiple nociceptive regions, particularly within obscure operculoinsular areas, underlying multidimensional pain processing remains elusive. This study aims to establish the fundamental organization between somatosensory and insular cortices in routing nociceptive information. By employing an integrated multimodal approach of high-field fMRI, intracranial electrophysiology, and transsynaptic viral tracing in rats, we observed a hierarchically organized connection of S1/S2 → posterior insula → anterior insula in routing nociceptive information. The directional nociceptive pathway determined by early fMRI responses was consistent with that examined by early evoked LFP, intrinsic effective connectivity, and anatomical projection, suggesting fMRI could provide a valuable facility to discern directional neural circuits in animals and humans non-invasively. Moreover, our knowledge of the nociceptive hierarchical organization of somatosensory and insular cortices and the interface role of the posterior insula may have implications for the development of targeted pain therapies.

An iteratively reweighted steered response power approach to multisource localization using a distributed microphone network.

The steered response power (SRP) with phase transform algorithm has been demonstrated to be robust against reverberation and noise for single-source localization. However, when this algorithm is applied to multisource localization (MSL), the "peak missing problem" can occur, namely, that some sources dominate over others over short time intervals, resulting in fewer significant SRP peaks being found than the true number of sources. This problem makes it difficult to detect all the sources among the available SRP peaks. We propose an iteratively reweighted steered response power (IR-SRP) approach that effectively solves the "peak missing problem" and achieves robust MSL in reverberant noisy environments. The initial IR-SRP localization function is computed over the time-frequency (T-F) bins selected by a combination of two weighting schemes, one using coherence, and the other using signal-to-noise ratio. When iterating, our method finds the significant SRP peaks for the dominant sources and eliminates the T-F bins contributed by these sources using inter-channel phase difference information. As a result, the remaining sources can be found in subsequent iterations among the remaining T-F bins. The proposed IR-SRP method is demonstrated using both simulated and measured experiment data.

Impact of Enhanced Emergency Nursing Processes on the Rescue Outcomes of Emergency Patients with Chest Pain.

Background: Chest pain, a sudden and perilous symptom, is frequently encountered in the emergency department. Prompt and efficient first-aid measures and nursing interventions are crucial for effectively rescuing emergency patients experiencing chest pain. Objective: This study aims to investigate the impact of an enhanced emergency nursing process on the rescue outcomes of emergency patients with chest pain. Design: A randomized controlled study was conducted. Setting: The research was conducted at Suzhou Hospital of Integrated Traditional Chinese and Western Medicine. Participants: A total of 90 emergency chest pain patients admitted between December 2021 and June 2022 were selected and divided into two groups, with 45 cases in each group. Interventions: The control group received routine emergency nursing, while the observation group underwent an improved emergency nursing protocol. Primary Outcome Measures: (1) Treatment initiation time, emergency rescue time, recovery time of vital signs, and hospital stay; (2) curative effect; (3) pain scores; (4) incidence of adverse events; and (5) patient satisfaction. Results: Compared to the control group, the observation group exhibited shorter treatment initiation time, emergency rescue time, recovery time of vital signs, and hospital stay (P < .05). The effective rate in the observation group was higher (P < .05), and pain scores were lower at 30 min, 60 min, 120 min, and 240 min post-rescue (P < .05). The occurrence of adverse events was reduced in the observation group (P = .005), and patient satisfaction was higher at discharge (P < .05). Conclusion: The enhanced emergency nursing process effectively reduces the clinical rescue time for emergency patients with chest pain, enhances rescue efficiency, seizes crucial opportunities for saving lives, and improves patient satisfaction. These findings have significant positive implications for clinical applications.

Melanin-Concentrating Hormone Is Associated With Delayed Neurocognitive Recovery in Older Adult Patients With Preoperative Sleep Disorders Undergoing Spinal Anesthesia.

BACKGROUND: Aging and preoperative sleep disorders are the main risk factors affecting postoperative cognitive outcomes. However, the pathogenesis of delayed neurocognitive recovery after surgery remains ambiguous, and there is still a lack of potential biomarkers for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders. Our study aimed to explore the relationship between melanin-concentrating hormone (MCH) and delayed neurocognitive recovery early after surgery in older adult patients with preoperative sleep disorders. METHODS: In this monocentric prospective observational study, 156 older adult patients (aged 65 years or older) with preoperative sleep disorders undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) were included at an academic medical center in Inner Mongolia, China, from October 2021 to November 2022, and all patients underwent spinal anesthesia. The Pittsburgh Sleep Quality Index (PSQI) was applied to assess the preoperative sleep quality of all patients, and preoperative sleep disorders were defined as a score of PSQI >5. We measured the levels of cerebrospinal fluid (CSF) MCH and plasma MCH of all patients. The primary outcome was delayed neurocognitive recovery early after surgery. All patients received cognitive function assessment through the Montreal Cognitive Assessment (MoCA) 1 day before and 7 days after surgery (postoperative day 7 [POD7]). Delayed neurocognitive recovery was defined as a score of POD7 MoCA <26. The potential confounders included variables with P < .2 in the univariate logistic analysis, as well as the important risk factors of delayed neurocognitive recovery reported in the literature. Multivariable logistic regression model based on the Enter method assessed the association of MCH and delayed neurocognitive recovery in older adult patients with preoperative sleep disorders. RESULTS: Fifty-nine (37.8%) older adult patients with preoperative sleep disorders experienced delayed neurocognitive recovery at POD7. Increase in CSF MCH levels (odds ratio [OR] for an increase of 1 pg/mL = 1.16, 95% confidence interval [CI], 1.09-1.23, P < .001) and decrease in plasma MCH levels (OR for an increase of 1 pg/mL = 0.92, 95% CI, 0.86-0.98, P = .003) were associated with delayed neurocognitive recovery, after adjusting for age, sex, education, baseline MoCA scores, American Society of Anesthesiologists (ASA) grade, and coronary heart disease (CHD). CONCLUSIONS: In older adult patients with preoperative sleep disorders, MCH is associated with the occurrence of delayed neurocognitive recovery after surgery. Preoperative testing of CSF MCH or plasma MCH may increase the likelihood of identifying the high-risk population for delayed neurocognitive recovery in older adult patients with preoperative sleep disorders.

Analysis of bioactive components and synergistic action mechanism of ShuGan-QieZhi Capsule for treating non-alcoholic fatty liver disease.

BACKGROUND: ShuGan-QieZhi capsule (SGQZC) is a traditional Chinese preparation used to treat hyperlipidemia and obesity, even non-alcoholic fatty liver disease (NAFLD). However, its therapeutic effects, main bioactive ingredients, as well as potential mechanisms for NAFLD are still unclear. PURPOSE: To investigate the pharmacological effect, main active ingredients, and mechanisms of SGQZC against high-fat diet (HFD)-induced NAFLD in mice. METHODS: NAFLD models were established by feeding C57BL/6 J mice an HFD for 24 weeks. From the 12th week, HFD-fed mice received daily gavage of either SGQZC or silibinin for 12 weeks. Hepatic hypertrophy parameters, along with hepatic and systemic lipid metabolism changes in NAFLD mice, were assessed. Oil red O and histopathological staining techniques determined lipid accumulation and liver injury severity. qRT-PCR analysis measured the expression of genes tied to liver lipid metabolism and inflammation. HPLC-MS/MS identified the primary components of SGQZC in the serum. Human normal hepatocytes (LO2) and hepatic stellate cells (LX-2) were used to screen SGQZC's bioactive ingredients. Network pharmacological analysis, transcriptomics, and western blotting delved into SGQZC's synergistic mechanisms against NAFLD. RESULTS: SGQZC ameliorated abnormal lipid metabolism and liver hypertrophy in mice with HFD-induced NAFLD, consequently reducing hepatic lipid accumulation, inflammatory cell infiltration, and liver impairment. Eight crucial components of SGQZC were detected in serum using HPLC-MS/MS and were found to effectively attenuate lipid accumulation and inflammation in liver cells. Further investigation indicated that SGQZC modulates MAPK pathway and AKT/NF-κB pathway, subsequently improving lipid metabolism and inflammation. CONCLUSION: SGQZC alleviates NAFLD by synergistically modulating the MAPK-mediated lipid metabolism and inhibiting AKT/NF-κB pathways-mediated inflammation. Our findings reveal the enormous potential of SGQZC for the treatment of NAFLD, providing a possible new clinical therapeutic strategy.

Surface-Immobilized ZnNx Sites as High-Performance Catalysts for Continuous Flow Knoevenagel Condensation in Water.

By immobilizing the metal complex on the substrate surface, our previous results have demonstrated that heterogeneous catalysts with well-dispersed active MNC (metal-nitrogen-carbon) sites can be prepared in a rational and efficient manner. In this study, we employed agarose aerogel (AA) as the substrate to illustrate a straightforward strategy for immobilizing ZnNx sites on the surface. Under relatively low temperatures, the amine group of the ligand condenses with the surface carbonyl group generated in situ, resulting in the surface immobilized Zn sites. This can be supported by the IR, PXRD, and XPS data. Comprehensive characterization methods, including synchrotron powder XRD and spherical aberration-corrected TEM, confirmed the absence of ZnNx site aggregation in the surface immobilization process, even with a high Zn content (up to 8 wt %). The immobilized ZnNx sites exhibited high catalytic performance in Knoevenagel condensation, and α,ß-unsaturated compounds were obtained with high yield in both batch and continuous flow reactions. AA-ZnNx-200 showed the best catalytic activity, which was processed under 200 °C with a Zn content of 4.62 wt %. The immobilized ZnNx sites activated both the aldehyde and nitrile substrates, which were quantitatively converted into the corresponding α,ß-unsaturated compounds, with water as the solvent at room temperature. In continuous flow reaction conditions, a conversion rate up to 99% can be achieved with malononitrile. This heterogeneous catalyst can be facilely produced with quantitative yield in a large scale from cheap starting material under mild conditions. No catalyst deactivation was observed after seven batch reaction cycles or 80 h of continuous flow reaction, indicating its high robustness under catalytic reaction conditions. This catalyst enables a separation-free, energy-saving, and environment-friendly production process, offering a practical way for the industrial production.

Anti-NMDAR antibodies, the blood-brain barrier, and anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an antibody-related autoimmune encephalitis. It is characterized by the existence of antibodies against NMDAR, mainly against the GluN1 subunit, in cerebrospinal fluid (CSF). Recent research suggests that anti-NMDAR antibodies may reduce NMDAR levels in this disorder, compromising synaptic activity in the hippocampus. Although anti-NMDAR antibodies are used as diagnostic indicators, the origin of antibodies in the central nervous system (CNS) is unclear. The blood-brain barrier (BBB), which separates the brain from the peripheral circulatory system, is crucial for antibodies and immune cells to enter or exit the CNS. The findings of cytokines in this disorder support the involvement of the BBB. Here, we aim to review the function of NMDARs and the relationship between anti-NMDAR antibodies and anti-NMDAR encephalitis. We summarize the present knowledge of the composition of the BBB, especially by emphasizing the role of BBB components. Finally, we further provide a discussion on the impact of BBB dysfunction in anti-NMDAR encephalitis.

Smart Ratiometric SERS Nanoprobe for Real-Time Monitoring Hydrogen Peroxide in Living Cells during NADH Treatment Associated with Ferroptosis.

Studying the oxidative stress, especially the reactive oxygen species (ROS) response of ferroptosis, is crucial for the diagnosis and treatment of cancer based on ferroptosis. However, reliable quantitative analysis of intracellular ROS in cancer treatment for drug screening is still a challenge. Herein, a superior ratiometric SERS nanoprobe was developed for in situ, real-time, and highly sensitive detection of content variation of H2O2 within living cells. The SERS nanoprobe was prepared by coassembly of the internal standard molecule p-mercaptobenzonitrile and the reporter molecule p-mercaptophenylboronic acid on the surface of gold nanoparticles, used for synergistic calibration and detection of H2O2, which enables reliable detection of the true content of intracellular H2O2 without the interference of other substances in cells. Based on the nanoprobe, we found that the level of intracellular H2O2 of cancer cells was increased after the nicotinamide adenine dinucleotide (NADH) treatment, with a dose-dependence to the concentration of NADH. High doses of NADH (above 20 mM) can induce cell death by means of ferroptosis associated with the level elevation of intracellular lipid hydroperoxides. This study highlights the potential of the SERS nanoprobe for tracking content variation of cellular H2O2 and understanding its roles in screening new anticancer drugs.