Full Selectivity Control over the Catalytic Hydrogenation of Nitroaromatics into Six Products.

A full selectivity control over the catalytic hydrogenation of nitroaromatics leads to the production of six possible products, i.e., nitroso, hydroxylamine, azoxy, azo, hydrazo or aniline compounds, which has however not been achieved in the field of heterogeneous catalysis. Currently, there is no sufficient evidence to support that the catalytic hydrogenation of nitroaromatics with the use of heterogeneous metal catalysts would follow the Haber's mechanistic scheme based on electrochemical reduction. We now demonstrate in this work that it is possible to fully control the catalytic hydrogenation of nitroaromatics into their all six products using a single catalytic system under various conditions. Employing SnO2-supported Pt nanoparticles facilitated by the surface coordination of ethylenediamine and vanadium species enabled this unprecedented selectivity control. Through systematic investigation into the controlled production of all products and their chemical reactivities, we have constructed a detailed reaction network for the catalytic hydrogenation of nitroaromatics. Crucially, the application of oxygen-isolated characterization techniques proved indispensable in identifying unstable compounds such as nitroso, hydroxylamine, hydrazo compounds. The insights gained from this research offer invaluable guidance for selectively transforming nitroaromatics into a wide array of functional N-containing compounds, both advancing fundamental understanding and fostering practical applications in various fields.

MOF-Derived Nanoparticles with Enhanced Acoustical Performance for Efficient Mechano-Sonodynamic Therapy.

Ultrasound (US) generates toxic reactive oxygen species (ROS) by acting on sonosensitizers for cancer treatment, and the mechanical damage induced by cavitation effects under US is equally significant. Therefore, designing a novel sonosensitizer that simultaneously possesses efficient ROS generation and enhanced mechanical effects is promising. In this study, carbon-doped zinc oxide nanoparticles (C-ZnO) are constructed for mechano-sonodynamic cancer therapy. The presence of carbon (C) doping optimizes the electronic structure, thereby enhancing the ROS generation triggered by US, efficiently inducing tumor cell death. On the other hand, the high specific surface area and porous structure brought about by C doping enable C-ZnO to enhance the mechanical stress induced by cavitation bubbles under US irradiation, causing severe mechanical damage to tumor cells. Under the dual effects of sonodynamic therapy (SDT) and mechanical therapy mediated by C-ZnO, excellent anti-tumor efficacy is demonstrated both in vitro and in vivo, along with a high level of biological safety. This is the first instance of utilizing an inorganic nanomaterial to achieve simultaneous enhancement of ROS production and US-induced mechanical effects for cancer therapy. This holds significant importance for the future development of novel sonosensitizers and advancing the applications of US in cancer treatment.

Treatment of Tislelizumab-Induced Toxic Epidermal Necrolysis and Agranulocytosis: A Case Report and Literature Review.

BACKGROUND: Non-small Cell Lung Cancer (NSCLC) makes up about 85% of lung cancer cases, mainly adenocarcinoma and squamous cell carcinoma. Recently, PD-1 inhibitors have become crucial in NSCLC treatment, significantly enhancing survival for some. However, side effects, like skin reactions and hematotoxicity, limit their use, with drug-induced TEN and immunotherapy-induced agranulocytosis as severe adverse effects. CASE PRESENTATION: Herein, we have reported the case of a 75-year-old male diagnosed with metastatic Lung Squamous cell Carcinoma (LUSC) in the left lung. He received first-line treatment with one cycle of tislelizumab in combination with nab-paclitaxel and carboplatin, after which he developed Toxic Epidermal Necrolysis (TEN) and granulocytopenia. To address these two serious immune-related Adverse Events (irAEs), the patient was administered methylprednisolone in combination with gamma globulin for TEN and dexamethasone in combination with G-CSF for agranulocytosis. Antibiotics were also administered according to the patient's medication regimen. After treatment, the patient recovered and was discharged from the hospital. It was also noted that the lung tumor condition improved. CONCLUSION: Effective management of severe immune-related side effects from tislelizumab, including TEN and agranulocytosis, can be partly achieved through steroids, gamma globulin, GCSF, and antibiotics. This strategy not only alleviates these adverse effects, but also potentially improves tumor conditions, highlighting the crucial role of vigilant monitoring and management in immunotherapy.

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis.

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

Predicting haemorrhagic transformation through serum biochemical indices for patients after endovascular treatment: a retrospective study.

INTRODUCTION: The aim of this study was to determine the serum biochemical markers that can predict the risk of haemorrhagic transformation (HT) before and after endovascular treatment (EVT). MATERIAL AND METHODS: This study included patients with anterior circulation large vessel occlusion (ACLVO) who underwent EVT within six hours of symptom onset between September 2017 and September 2022. These patients were retrospectively categorised into two groups: an HT group and a No-HT group. RESULTS: A total of 180 patients were included in the study, of whom 55 (30.6%) had HT. The monocyte count before EVT (p = = 0.005, OR = 0.694, 95% CI 0.536-0.898), the activated partial thromboplastin time before EVT (p = 0.009, OR = 0.186, 95% CI 0.699-0.952), and the eosinophil count after EVT (p = 0.038, OR = 0.001, 95% CI 0.000-0.018) were all found to be independent predictors of HT, with warning values of 6.65%, 22.95 seconds, and 0.035*10^9/L, respectively. When compared to prediction using only demographic data [AUC = 0.662,95% CI (0.545, 0.780)], adding biochemical indices before EVT [AUC = 0.719,95% CI (0.617, 0.821)], adding biochemical indices after EVT [AUC = 0.670,95% CI (0.566, 0.773)], and adding both [AUC = 0.778,95% CI (0.686, 0.870)], the prediction efficiency of HT was improved among all three combinations, with no statistical significance. CONCLUSIONS: The levels of serum biochemical markers were found to show significant changes before and after EVT in ACLVO patients. A combination of demographic data and serum biochemical markers proved to be effective in predicting the occurrence of HT in patients with ACLVO who underwent EVT.

Age-related changes after intracerebral hemorrhage: a comparative proteomics analysis of perihematomal tissue.

The risk factors and causes of intracerebral hemorrhage (ICH) and the degree of functional recovery after ICH are distinct between young and elderly patients. The increasing incidence of ICH in young adults has become a concern; however, research on the molecules and pathways involved ICH in subjects of different ages is lacking. In this study, tandem mass tag (TMT)-based proteomics was utilized to examine the protein expression profiles of perihematomal tissue from young and aged mice 24 h after collagenase-induced ICH. Among the 5,129 quantified proteins, ICH induced 108 and 143 differentially expressed proteins (DEPs) in young and aged mice, respectively; specifically, there were 54 common DEPs, 54 unique DEPs in young mice and 89 unique DEPs in aged mice. In contrast, aging altered the expression of 58 proteins in the brain, resulting in 39 upregulated DEPs and 19 downregulated DEPs. Bioinformatics analysis indicated that ICH activated different proteins in complement pathways, coagulation cascades, the acute phase response, and the iron homeostasis signaling pathway in mice of both age groups. Protein-protein interaction (PPI) analysis and ingenuity pathway analysis (IPA) demonstrated that the unique DEPs in the young and aged mice were related to lipid metabolism and carbohydrate metabolism, respectively. Deeper paired-comparison analysis demonstrated that apolipoprotein M exhibited the most significant change in expression as a result of both aging and ICH. These results help illustrate age-related protein expression changes in the acute phase of ICH.

Frustrated Lewis pairs on pentacoordinated Al3+-enriched Al2O3 promote heterolytic hydrogen activation and hydrogenation.

As an emerging class of metal-free catalysts, frustrated Lewis pairs (FLPs) catalysts have been greatly constructed and applied in many fields. Homogeneous FLPs have witnessed significant development, while limited heterogeneous FLPs catalysts are available. Herein, we report that heterogeneous FLPs on pentacoordinated Al3+-enriched Al2O3 readily promote the heterolytic activation of H2 and thus hydrogenation catalysis. The defect-rich Al2O3 was prepared by simple calcination of a carboxylate-containing Al precursor. Combinatorial studies confirmed the presence of rich FLPs on the surface of the defective Al2O3. In contrast to conventional alumina (γ-Al2O3), the FLP-containing Al2O3 can activate H2 in the absence of any transition metal species. More importantly, H2 was activated by surface FLPs in a heterolytic pathway, leading to the hydrogenation of styrene in a stepwise process. This work paves the way for the exploration of more underlying heterogeneous FLPs catalysts and further understanding of accurate active sites and catalytic mechanisms of heterogeneous FLPs at the molecular level.

Adolescent male rats show altered gut microbiota composition associated with depressive-like behavior after chronic unpredictable mild stress: Differences from adult rats.

Accumulating evidence reveals the metabolism and neurotransmitter systems are different in major depressive disorder (MDD) between adolescent and adult patients; however, much is still unknown from the gut microbiome perspective. To minimize confounding factors such as geographical location, ethnicity, diet, and drugs, we investigated the gut microbial differences between adolescent and adult male Sprague-Dawley rats. We exposed the adolescent rats to chronic unpredictable mild stress (CUMS) for 3 weeks and assessed their behavior using the sucrose preference test (SPT), open field test (OFT), and forced swimming test (FST). We collected and sequenced fecal samples after the behavioral tests and compared them with our previous data on adult rats. Both adolescent and adult CUMS rats exhibited reduced sucrose preference in SPT, reduced total distance in OFT, and increased immobility time in FST. Moreover, compared to their respective controls, the adolescent CUMS rats had distinct amplicon sequence variants (ASVs) mainly in the Muribaculaceae family, Bacteroidetes phylum, while the adult CUMS rats had those in the Lachnospiraceae family, Firmicutes phylum. In the adolescent group, the Muribaculaceae negatively correlated with FST and positively correlated with SPT and OFT. In the adult group, the different genera in the Lachnospiraceae showed opposite correlations with FST. Furthermore, the adolescent CUMS rats showed disrupted microbial functions, such as "Xenobiotics biodegradation and metabolism" and "Immune system", while the adult CUMS rats did not. These results confirmed the gut microbiota differences between adolescent and adult rats after CUMS modeling and provided new insight into the age-related influence on depression models.

64 picosecond time resolved time-correlated single photon counting imaging.

High-speed imaging of dynamic scenes is a challenging and important task in many applications. However, conventional imaging methods based on charge coupled devices or complementary metal oxide semiconductors have limitations in temporal resolution and photon sensitivity. To address this problem, we propose a novel high-speed imaging scheme that combines single-pixel imaging with single photon detection and time-correlated single photon counting. Our scheme can achieve high-speed imaging with 64 ps resolution by repeating the motion scenes and using binary outputs from single photon detectors. We demonstrate our scheme by reconstructing the switching process of a digital micro-mirror device and a liquid crystal spatial light modulator. Our scheme can be further improved to 1 ps resolution by using a more accurate time-correlated single photon counting system. Moreover, our scheme can adapt to different speed scenes by adjusting the temporal resolution and reducing the sampling time. Our high temporal resolution imaging scheme further expands the application areas of single-pixel imaging and provides solutions for scenes requiring single photon detection and higher temporal resolution, such as reproducible chemical reaction processes imaging, cellular or sub-cellular bio imaging, single-molecule imaging of rotary motors, high-speed equipment inspection, and other periodic high-speed scenes imaging.

Neuronal small extracellular vesicles carrying miR-181c-5p contribute to the pathogenesis of epilepsy by regulating the protein kinase C-δ/glutamate transporter-1 axis in astrocytes.

Information exchange between neurons and astrocytes mediated by extracellular vesicles (EVs) is known to play a key role in the pathogenesis of central nervous system diseases. A key driver of epilepsy is the dysregulation of intersynaptic excitatory neurotransmitters mediated by astrocytes. Thus, we investigated the potential association between neuronal EV microRNAs (miRNAs) and astrocyte glutamate uptake ability in epilepsy. Here, we showed that astrocytes were able to engulf epileptogenic neuronal EVs, inducing a significant increase in the glutamate concentration in the extracellular fluid of astrocytes, which was linked to a decrease in glutamate transporter-1 (GLT-1) protein expression. Using sequencing and gene ontology (GO) functional analysis, miR-181c-5p was found to be the most significantly upregulated miRNA in epileptogenic neuronal EVs and was linked to glutamate metabolism. Moreover, we found that neuronal EV-derived miR-181c-5p interacted with protein kinase C-delta (PKCδ), downregulated PKCδ and GLT-1 protein expression and increased glutamate concentrations in astrocytes both in vitro and in vivo. Our findings demonstrated that epileptogenic neuronal EVs carrying miR-181c-5p decrease the glutamate uptake ability of astrocytes, thus promoting susceptibility to epilepsy.

Prediction of Death in Intracerebral Hemorrhage Patients After Minimally Invasive Surgery by Vital Signs and Blood Glucose.

OBJECTIVE: This study examined the impact of vital signs and blood glucose levels on the long-term prognosis of intracerebral hemorrhage (ICH) patients treated with minimally invasive surgery (MIS). METHODS: The patients diagnosed with ICH and treated with MIS within 24 hours of admission at the ∗∗ Hospital between January 2020 and October 2021 were included. The relationship between a range of indicators, including vital signs, blood glucose levels, and patient mortality at discharge and 3 or 12 months postdischarge were analyzed. RESULTS: A total of 195 consecutive patients were included, of which 16 patients passed away during hospitalization, 29 and 34 within 3 and 12 months postdischarge, respectively. The multivariate analysis revealed that hospital death positively correlated with age ≥66.50 years, fasting blood glucose ≥8.25 mmol/L on the third day after MIS, systolic blood pressure ≥166.00 mmHg on the third day, and heart rate ≥89.50 beats/min at discharge (area under the curve [AUC] = 0.927). Death at 3 months positively correlated with male sex, blood glucose before dinner ≥8.15 mmol/L on the second day after MIS, body temperature ≥36.95°C at discharge, and heart rate ≥89.50 beats/minute at discharge (AUC = 0.810). Death at 12 months positively correlated with age ≥61.50 years, body temperature ≥36.95°C at discharge, and heart rate ≥92.50 beats/min on the third day after MIS (AUC = 0.824). CONCLUSIONS: The prognosis of ICH patients after MIS is closely related to their vital signs and blood glucose levels at various stages of hospitalization.

Oral D-ribose causes depressive-like behavior by altering glycerophospholipid metabolism via the gut-brain axis.

Our previous work has shown that D-ribose (RIB)-induced depressive-like behaviors in mice. However, the relationship between variations in RIB levels and depression as well as potential RIB participation in depressive disorder is yet unknown. Here, a reanalysis of metabonomics data from depressed patients and depression model rats is performed to clarify whether the increased RIB level is positively correlated with the severity of depression. Moreover, we characterize intestinal epithelial barrier damage, gut microbial composition and function, and microbiota-gut-brain metabolic signatures in RIB-fed mice using colonic histomorphology, 16 S rRNA gene sequencing, and untargeted metabolomics analysis. The results show that RIB caused intestinal epithelial barrier impairment and microbiota-gut-brain axis dysbiosis. These microbial and metabolic modules are consistently enriched in peripheral (fecal, colon wall, and serum) and central (hippocampus) glycerophospholipid metabolism. In addition, three differential genera (Lachnospiraceae_UCG-006, Turicibacter, and Akkermansia) and two types of glycerophospholipids (phosphatidylcholine and phosphatidylethanolamine) have greater contributions to the overall correlations between differential genera and glycerophospholipids. These findings suggest that the disturbances of gut microbiota by RIB may contribute to the onset of depressive-like behaviors via regulating glycerophospholipid metabolism, and providing new insight for understanding the function of microbiota-gut-brain axis in depression.

Comparison of Perioperative Safety of Carotid Artery Stenting and Endarterectomy in the Treatment of Carotid Artery Stenosis: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Current management guidelines for the treatment of carotid stenosis are controversial. We performed this meta-analysis to evaluate the perioperative safety of carotid artery stenting (CAS) and endarterectomy. METHODS: We systematically searched EMBASE, PubMed, Web of Science, and the Cochrane Library from inception to November 10, 2022, for randomized controlled trials that compared CAS with carotid endarterectomy (CEA) among patients with carotid stenosis. The analyzed outcomes mainly included stroke, death, myocardial infarction (MI), cranial nerve palsy, the cumulative incidence of mortality, stroke, or MI and the cumulative incidence of death or stroke in the perioperative periods. The risk ratio (RR) and 95% confidence interval (95% CI) were calculated and pooled. Subgroup analyses were based on whether patients were symptomatic or asymptomatic. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. RESULTS: Seventeen randomized controlled trials with 12,277 participants (6514 and 5763 in the CAS and CEA groups, respectively) were included. Pooled analysis demonstrated that compared with CEA, CAS was associated with decreased risks of perioperative MI (RR = 0.47, 95% CI = 0.29∼0.77) and perioperative cranial nerve palsy (RR = 0.02, 95% CI = 0.01∼0.06) but higher risks of perioperative stroke (RR = 1.48, 95% CI = 1.18∼1.87) and cumulative incidence of death or stroke (RR = 1.52, 95% CI = 1.20∼1.93). CONCLUSIONS: The perioperative safety was equivalent between CAS and CEA. However, CEA may be preferred when considering both procedural safety and long-term efficacy in preventing recurrent stroke.

Self-Driven Electric Field Control of Orbital Electrons in AuPd Alloy Nanoparticles for Cancer Catalytic Therapy.

The free radical generation efficiency of nanozymes in cancer therapy is crucial, but current methods fall short. Alloy nanoparticles (ANs) hold promise for improving catalytic performance due to their inherent electronic effect, but there are limited ways to modulate this effect. Here, a self-driven electric field (E) system utilizing triboelectric nanogenerator (TENG) and AuPd ANs with glucose oxidase (GOx)-like, catalase (CAT)-like, and peroxidase (POD)-like activities is presented to enhance the treatment of 4T1 breast cancer in mice. The E stimulation from TENG enhances the orbital electrons of AuPd ANs, resulting in increased CAT-like, GOx-like, and POD-like activities. Meanwhile, the catalytic cascade reaction of AuPd ANs is further amplified after catalyzing the production of H2 O2 from the GOx-like activities. This leads to 89.5% tumor inhibition after treatment. The self-driven E strategy offers a new way to enhance electronic effects and improve cascade catalytic therapeutic performance of AuPd ANs in cancer therapy.

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.

Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.

Nomogram for Estimation of Acute Liver Failure Risk in Spontaneous Ruptured Hepatocellular Carcinoma.

Purpose: Acute liver failure (ALF) is a severe complication of spontaneous ruptured hepatocellular carcinoma (SRHCC) that requires accurate prediction for effective treatment strategies. We aimed to develop a predictive nomogram to estimate the risk of ALF in patients with SRHCC undergoing treatment. Patients and Methods: We performed a retrospective analysis of historical data from 284 patients diagnosed with SRHCC at the First Hospital of Jilin University over the past decade. Variables were selected through univariate and multivariate logistic regression analyses, and a predictive nomogram was constructed. We evaluated its predictive accuracy against the Child-Pugh Score, R.MELD, and ALBI by assessing discrimination, calibration, and net clinical benefit. Results: Among the 284 patients, 65 developed ALF. The risk factors identified for model development included largest tumor size (LTS), platelet counts, prolonged prothrombin time, and elevated serum α-fetoprotein levels. The nomogram exhibited high accuracy in predicting ALF risk with a C-index of 0.91 (0.87-0.95). The Delong test showed a significant difference between the nomogram and the other three models (p<0.05). The calibration curve for the nomogram fit well, and the decision curve analysis revealed superior net benefit. The optimal cut-off point for the nomogram was determined to be 40, yielding sensitivity, specificity, positive predictive value, and negative predictive value of 83.10%, 87.20%, 65.90% and 94.60%, respectively. Conclusion: The nomogram we developed provides an optimized tool for predicting ALF in SRHCC patients. Its application can help determine individual patient's risk of ALF, enabling more rational and personalized treatment strategies.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

Vacancy Augmented Piezo-Sonosensitizer for Cancer Therapy.

Sonodynamic therapy (SDT) has been widely reported as a noninvasive and high-penetration therapy for cancer; however, the design of an efficient sonosensitizer remains an urgent need. To address this issue, molybdenum disulfide nanoflowers (MoS2 NF) as piezo-sonosensitizers and introduced sulfur vacancies on the MoS2 NF (Sv-MoS2 NF) to improve their piezoelectric property for cancer therapy are designed. Under ultrasonic mechanical stress, the Sv-MoS2 NF resulted in piezoelectric polarization and band tilting, which enhanced the charge carrier separation and migration. This resulted in an improved catalytic reaction for reactive oxygen species (ROS) production, ultimately enhancing the SDT performance. Thanks to the high efficiency of ROS generation, the Sv-MoS2 NF have demonstrated a good anticancer effect in vitro and in vivo. Following a systematic evaluation, Sv-MoS2 NF also demonstrated good biocompatibility. This novel piezo-sonosensitizer and vacancy engineering strategy provides a promising new approach for achieving efficient SDT.

Integrating spatial and single-nucleus transcriptomic data elucidates microglial-specific responses in female cynomolgus macaques with depressive-like behaviors.

Major depressive disorder represents a serious public health challenge worldwide; however, the underlying cellular and molecular mechanisms are mostly unknown. Here, we profile the dorsolateral prefrontal cortex of female cynomolgus macaques with social stress-associated depressive-like behaviors using single-nucleus RNA-sequencing and spatial transcriptomics. We find gene expression changes associated with depressive-like behaviors mostly in microglia, and we report a pro-inflammatory microglia subpopulation enriched in the depressive-like condition. Single-nucleus RNA-sequencing data result in the identification of six enriched gene modules associated with depressive-like behaviors, and these modules are further resolved by spatial transcriptomics. Gene modules associated with huddle and sit alone behaviors are expressed in neurons and oligodendrocytes of the superficial cortical layer, while gene modules associated with locomotion and amicable behaviors are enriched in microglia and astrocytes in mid-to-deep cortical layers. The depressive-like behavior associated microglia subpopulation is enriched in deep cortical layers. In summary, our findings show cell-type and cortical layer-specific gene expression changes and identify one microglia subpopulation associated with depressive-like behaviors in female non-human primates.

Inhibition of ANXA2 activity attenuates epileptic susceptibility and GluA1 phosphorylation.

INTRODUCTION: Annexin A2 (ANXA2) participates in the pathology of a variety of diseases. Nevertheless, the impact of ANXA2 on epilepsy remains to be clarified. AIMS: Hence, the study aimed at investigating the underlying role of ANXA2 in epilepsy through behavioral, electrophysiological, and pathological analyses. RESULTS: It was found that ANXA2 was markedly upregulated in the cortical tissues of temporal lobe epilepsy patients (TLE), kainic acid (KA)-induced epilepsy mice, and in a seizure-like model in vitro. ANXA2 silencing in mice suppressed first seizure latency, number of seizures, and seizure duration in behavioral analysis. In addition, abnormal brain discharges were less frequent and shorter in the hippocampal local field potential (LFP) record. Furthermore, the results showed that the frequency of miniature excitatory postsynaptic currents was decreased in ANXA2 knockdown mice, indicating that the excitatory synaptic transmission is reduced. Co-immunoprecipitation (COIP) experiments demonstrated that ANXA2 interacted with the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit GluA1. Moreover, ANXA2 knockdown decreased GluA1 expression on the cell surface and its phosphorylation onserine 831 and serine 845, related to the decreased phosphorylation levels mediated by protein kinases A and C (PKA and PKC). CONCLUSIONS: This study covers a previously unknown and key function of ANXA2 in epilepsy. These findings indicate that ANXA2 can regulate excitatory synaptic activity mediated by AMPAR subunit GluA1 to improve seizure activity, which can provide novel insights for the treatment and prevention of epilepsy.