Non B Cell-Derived Immunoglobulin, A Brighter Horizon for the Future.

The canonical theory of immunology stating that "Immunoglobulin (Ig) is produced by B lymphocytes and exerts antibody activity" has been established since the 1970s. However, the discovery of non B cell-derived Igs (non B-Igs), which can exert multiple biological activities in addition to their antibody activities, necessitates a reevaluation of the classic concept of Ig. This has been documented with a number of characteristics related to their structure, modification, genetic regulation as well as the functions associated with clinical conditions, particularly multiple cancers. The discovery of non B-Ig provides us with a new perspective to better understand not only basic immunology, but also various Ig-related clinical manifestations including autoimmune diseases, chronic inflammation, and anaphylaxis. Notably, non B-Ig can directly promote the occurrence of malignant tumours.

Sodium-glucose cotransporter-2 inhibitors and abnormal serum potassium: a real-world, pharmacovigilance study.

BACKGROUND: New trials indicated a potential of sodium-glucose cotransporter-2 inhibitors (SGLT2i) to reduce hyperkalemia, which might have important clinical implications, but real-world data are limited. Therefore, we examined the effect of SGLT2i on hyper- and hypokalemia occurrence using the FDA adverse event reporting system (FAERS). METHODS: The FAERS database was retrospectively queried from 2004q1 to 2021q3. Disproportionality analyses were performed based on the reporting odds ratio (ROR) and 95% confidence interval (CI). RESULTS: There were 84 601 adverse event reports for SGLT2i and 1 321 186 reports for other glucose-lowering medications. The hyperkalemia reporting incidence was significantly lower with SGLT2i than with other glucose-lowering medications (ROR, 0.83; 95% CI, 0.79-0.86). Reductions in hyperkalemia reports did not change across a series of sensitivity analyses. Compared with that with renin-angiotensin-aldosterone system inhibitors (RAASi) alone (ROR, 4.40; 95% CI, 4.31-4.49), the hyperkalemia reporting incidence was disproportionally lower among individuals using RAASi with SGLT2i (ROR, 3.25; 95% CI, 3.06-3.45). Compared with that with mineralocorticoid receptor antagonists (MRAs) alone, the hyperkalemia reporting incidence was also slightly lower among individuals using MRAs with SGLT-2i. The reporting incidence of hypokalemia was lower with SGLT2i than with other antihyperglycemic agents (ROR, 0.79; 95% CI, 0.75-0.83). CONCLUSION: In a real-world setting, hyperkalemia and hypokalemia were robustly and consistently reported less frequently with SGLT2i than with other diabetes medications. There were disproportionally fewer hyperkalemia reports among those using SGLT-2is with RAASi or MRAs than among those using RAASi or MRAs alone.

Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy.

The extracellular matrix (ECM) is critical for drug resistance in colorectal cancer (CRC). The abundant collagen within the ECM significantly influences tumor progression and matrix-mediated drug resistance (MMDR) by binding to discoidin domain receptor 1 (DDR1), but the specific mechanisms by which tumor cells modulate ECM via DDR1 and ultimately regulate TME remain poorly understand. Furthermore, overcoming drug resistance by modulating the tumor ECM remains a challenge in CRC treatment. In this study, a novel mechanism is elucidated by which DDR1 mediates the interactions between tumor cells and collagen, enhances collagen barriers, inhibits immune infiltration, promotes drug efflux, and leads to MMDR in CRC. To address this issue, a multistage drug delivery system carrying DDR1-siRNA and chemotherapeutic agents is employed to disrupt collagen barriers by silencing DDR1 in tumor, enhancing chemotherapy drugs diffusion and facilitating immune infiltration. These findings not only revealed a novel role for collagen-rich matrix mediated by DDR1 in tumor resistance, but also introduced a promising CRC treatment strategy.

Identification of Cuproptosis-related Gene Lipoyltransferase 1 as a Promising Biomarker in Oral Squamous Cell Carcinoma.

OBJECTIVE: To find efficient cuproptosis-related biomarkers to explore the oncogenesis and progression of oral squamous cell carcinoma (OSCC). METHODS: All the original data were downloaded from the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and Kaplan-Meier survival analysis were used to identify the gene related to survival. Tumor Immune Estimation Resource 2.0 (TIMER 2.0) was used to reveal the different expression of cuproptosis-related gene lipoyltransferase 1 (LIPT1) in various kinds of tumours. RESULTS: LIPT1, as a cuproptosis-related gene, was found to be differentially expressed in the OSCC group and the control group. It was also found to be related to the prognosis of OSCC. Pan cancer analysis showed LIPT1 was also involved in various kinds of tumours. CONCLUSION: All the results demonstrate that the cuproptosis-related gene LIPT1 is highly involved in the oncogenesis and progression of OSCC. These findings give new insight for further research into the cuproptosis-related biomarkers in OSCC.

Selective N-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh3/DDQ System.

We present a PPh3/DDQ-mediated regiospecific selective N-functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of N1-benzyl arylhydrazines and N2-acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, N1-benzlated products have also been successfully applied to the concise synthesis of N-substituted indoles and anticancer drug MDM2 inhibitor.

Loss of transient receptor potential channel 5 causes obesity and postpartum depression.

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of Trpc5 from oxytocin neurons in the hypothalamic paraventricular nucleus caused obesity in both sexes and postpartum depressive behavior in females, while Trpc5 overexpression in oxytocin neurons in knock-in mice reversed these phenotypes. We demonstrate that TRPC5 plays a pivotal role in mediating innate human behaviors fundamental to survival, including food seeking and maternal care.

Establishment and Validation of a Risk Prediction Model for Non-Invasive Ventilation Failure After Birth in Premature Infants with Gestational Age < 32 Weeks.

OBJECTIVES: This study was performed to construct and validate a risk prediction model for non-invasive ventilation (NIV) failure after birth in premature infants with gestational age < 32 weeks. METHODS: The data were derived from the multicenter retrospective study program - Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network from Jan 2019 to Dec 2021. The subjects finally included were preterm infants using NIV after birth with gestational age less than 32 weeks and admission age within 72 h. After screening by inclusion and exclusion criteria, 1436 babies were subsequently recruited in the study, including 1235 infants in the successful NIV group and 201 infants in the failed NIV group. RESULTS: (1) Gestational age, 5 min Apgar, Max FiO2 during NIV, and FiO2 fluctuation value during NIV were selected by univariate and multivariate analysis. (2) The area under the curve of the prediction model was 0.807 (95% CI: 0.767-0.847) in the training set and 0.825 (95% CI: 0.766-0.883) in the test set. The calibration curve showed good agreement between the predicted probability and the actual observed probability (Mean absolute error = 0.008 for the training set; Mean absolute error = 0.012 for the test set). Decision curve analysis showed good clinical validity of the risk model in the training and test cohorts. CONCLUSION: This model performed well on dimensions of discrimination, calibration, and clinical validity. This model can serve as a useful tool for neonatologists to predict whether premature infants will experience NIV failure after birth.

Oleic acid treatment of rice grains reduces the starch digestibility: Formation, binding state and fine structure of starch-lipid complexes.

Rice contains abundant starch and contributes to a rapid rise in postprandial blood glucose levels. Hence, it is crucial to directly modify rice grains for resistant starch (RS) content elevation while preserving their morphology. In this study, rice grains were treated with 6%-18% concentrations of oleic acid (OA) and 8-20 h of soaking time to promote the formation of starch-lipid complexes, thereby reducing rice digestibility. In OA-treated rice, the OA molecules exist in three binding states. OA-treated rice exhibited a significantly higher complexation index and OA content than natural rice. RS content increased from 20.50% to 32.46%. X-ray diffraction and NMR spectroscopy revealed the development of amylose-OA complexes within the rice grains and a V-crystalline structure of up to 3.62%. Raman spectroscopy and thermogravimetric analysis showed enhanced molecular ordering and structural stability of rice starch. Overall, OA treatment effectively promotes RS formation within rice grains, consequently reducing rice digestibility.

Multiomics analysis reveals serine catabolism as a potential therapeutic target for MELAS.

Mitochondrial disease is a devastating genetic disorder, with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and m.3243A>G being the most common phenotype and genotype, respectively. The treatment for MELAS patients is still less effective. Here, we performed transcriptomic and proteomic analysis in muscle tissue of MELAS patients, and discovered that the expression of molecules involved in serine catabolism were significantly upregulated, and serine hydroxymethyltransferase 2 (SHMT2) increased significantly in both the mRNA and protein levels. The SHMT2 protein level was also increased in myoblasts with m.3243A>G mutation, which was transdifferentiated from patients derived fibroblasts, accompanying with the decreased nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) ratio and cell viability. After treating with SHMT2 inhibitor (SHIN1), the NAD+/NADH ratio and cell viability in MELAS myoblasts increased significantly. Taken together, our study indicates that enhanced serine catabolism plays an important role in the pathogenesis of MELAS and that SHIN1 can be a potential small molecule for the treatment of this disease.

A portable inflatable soft wearable robot to assist the shoulder during industrial work.

Repetitive overhead tasks during factory work can cause shoulder injuries resulting in impaired health and productivity loss. Soft wearable upper extremity robots have the potential to be effective injury prevention tools with minimal restrictions using soft materials and active controls. We present the design and evaluation of a portable inflatable shoulder wearable robot for assisting industrial workers during shoulder-elevated tasks. The robot is worn like a shirt with integrated textile pneumatic actuators, inertial measurement units, and a portable actuation unit. It can provide up to 6.6 newton-meters of torque to support the shoulder and cycle assistance on and off at six times per minute. From human participant evaluations during simulated industrial tasks, the robot reduced agonist muscle activities (anterior, middle, and posterior deltoids and biceps brachii) by up to 40% with slight changes in joint angles of less than 7% range of motion while not increasing antagonistic muscle activity (latissimus dorsi) in current sample size. Comparison of controller parameters further highlighted that higher assistance magnitude and earlier assistance timing resulted in statistically significant muscle activity reductions. During a task circuit with dynamic transitions among the tasks, the kinematics-based controller of the robot showed robustness to misinflations (96% true negative rate and 91% true positive rate), indicating minimal disturbances to the user when assistance was not required. A preliminary evaluation of a pressure modulation profile also highlighted a trade-off between user perception and hardware demands. Finally, five automotive factory workers used the robot in a pilot manufacturing area and provided feedback.

Identification of antidepressant constituents from Xiangfu-chuanxiong herbal medicine pair via spectrum-effect relationship analyses, molecular docking and corticosterone-induced PC12 cells.

Herbal medicine pair, composed of two single herbs, is a relatively fixed minimum prescription unit in the traditional Chinese medicine's formula and has special significance in clinic. The combination of Xiangfu (the rhizoma of Cyperus rotundus L, XF) and Chuanxiong (the rhizoma of Ligusticum chuanxiong Hort, CX) has been recoded as an herbal medicine pair XF-CX in the Yuan Dynasty (1347 CE) of China and widely used in traditional Chinese medicine formula, including Chaihu Shugan San, which has been clinically used for treatment of depression. However, the optimal ratio of the XF-CX herbal medicine pair and its antidepressant constituents are still unclear. Herein, the antidepressive-like effects of XF-CX herbal medicine pairs with different ratios of XF and CX (2:1, 1:1, 1:2) were evaluated using behavioral despair animal models in mice, and then its potential antidepressant constituents were recognized by spectrum-effect relationship analyses. Finally, the potential antidepressant constituents of the XF-CX herbal medicine pair were validated by molecular docking with glucocorticoid receptor and corticosterone (CORT)-induced PC12 cell injury model. The results indicated that different ratios of XF-CX pairs had antidepressive-like effects, and the XF-CX (2:1) exhibited a more significant effect. Thirty-two potential antidepressant constituents in the XF-CX herbal medicine pair were screened out from the spectrum-effect relationship combined molecular docking analyses. Among them, senkyunolide A, cyperotundone, Z-ligustilide, and levistilide A were validated to have protective effects against CORT-induced injury in PC12 cells. Our findings not only obtained the optimal ratio of XF-CX in the herbal medicine pair for the treatment of depression but also its potential antidepressant constituents, which will benefit in elucidating the mechanism of action and promoting the application of the herbal medicine pair in the clinic.

Multimodal training with dual-task enhances immediate and retained effects on dual-task effects of gait speed not by cognitive-motor trade-offs in stroke survivors: a randomized controlled trial.

PURPOSE: Individuals who have experienced stroke may benefit from dual-task related training to improve gait speed performance. Whether noted improvements reflect true effects on gait or cognitive-motor trade-offs still remains unclear. Therefore, this study aimed to investigate the effects of dual-task training on dual-task effects of both walking and cognitive domains in stroke survivors. MATERIALS AND METHODS: Forty-four individuals with stroke were randomized to dual-task or single-task training groups. Both groups exercised three 60-minute sessions per week for 4 weeks. The primary outcomes were dual-task effects on gait speed and cognitive score. Outcomes were assessed before and after the intervention and 1-month follow-up. RESULTS: While both groups exhibited improvement in absolute gait speed under dual-task conditions, the dual-task training group demonstrated superior results by providing an additional gain on dual-task effects of gait speed. Compared to single-task training, dual-task training exhibited a significant improvement in dual-task effects of gait speed at post-treatment and follow-up. Regarding the dual-task effects on cognitive scores, no significant differences within and between groups after training were observed. CONCLUSION: Dual-task training enhances immediate and retained effects on the dual-task effects of gait speed in individuals with stroke, not by cognitive-motor trade-offs. TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. CLINICALTRIALS.GOV IDENTIFIER: NCT02686515.

Dual-task interference during walking has important consequences for stroke survivors to walk safely.Multimodal training with dual-task enhances immediate and retained effects on the dual-task effects of gait speed in individuals with stroke, not by cognitive-motor trade-offs.Clinicians are encouraged to incorporate multimodal training with dual-task into the exercise routines to enhance walking under dual-task conditions in stroke survivors.

A light-responsive neural circuit suppresses feeding.

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb → 5-HTDRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice.Significance statement Feeding behavior is influenced by a myriad of sensory inputs, but the impact of light exposure on feeding regulation has remained enigmatic. Here, we showed that light exposure diminishes food intake across both nocturnal and diurnal species. Delving deeper, our findings revealed that the LHb → 5-HTDRN neural circuit plays a pivotal role in mediating light-induced anorexia in mice. These discoveries not only enhance our comprehension of the intricate neuronal mechanisms governing feeding in response to light but also offer insights for developing innovative strategies to address obesity and eating disorders.

[Spatiotemporal Pattern and Influencing Factors of Thermal Environment Based on SEM Model: A Case Study in Xi'an Metropolitan Area].

The urban thermal environment is an important indicator for evaluating the ecological environment of a city. It directly affects the health of residents and the sustainable development of the urban economy. However, there is currently a lack of analysis on the impact pathways of the thermal environment considering both natural and human factors. Based on the MODIS MYD11A2 land surface temperature data, meteorological data, and human activity data of Xi'an metropolitan area in 2020, ArcGIS spatial geostatistical analysis was used to study the temporal and spatial distribution pattern of the thermal environment in different seasons, and redundancy analysis was utilized to select the main factors affecting the thermal environment. Then, structural equation modeling was used to quantify the direct and indirect effects of the dominant factors on the urban thermal environment. The results showed that:① The surface temperature in the Xi'an urban area showed a spatial pattern of higher temperatures in the north and lower temperatures in the south, with a decrease in temperature from the city center to the surrounding areas. The most severe heat environment pollution occurred in the summer. ② The redundancy analysis (RDA) results indicated that the main factors that affected the thermal environment were air temperature, impermeable surfaces, vegetation, and precipitation. ③ The results of the structural equation modeling (SEM) indicated that meteorological, surface, and anthropogenic factors affected the urban thermal environment mainly through direct pathways, which were much more important than all indirect pathways. Factors such as temperature, impervious surfaces, and point of interest density had a significant positive effect on the thermal environment (0.10 and 0.33). On the other hand, factors such as water bodies, precipitation, and vegetation had a significant negative effect on the thermal environment (-0.29 and -0.25). Human activities had a greater direct impact on nocturnal surface temperatures than surface and meteorological factors. Increasing economic efficiency is beneficial for mitigating the urban heat island effect. The results of the study can provide a reference for studying local climate change in urban heat islands and for the construction of green and ecologically livable urban environments.

Mechanistic prediction and validation of Brevilin A Therapeutic effects in Lung Cancer.

BACKGROUND: Traditional Chinese medicine (TCM) has been found widespread application in neoplasm treatment, yielding promising therapeutic candidates. Previous studies have revealed the anti-cancer properties of Brevilin A, a naturally occurring sesquiterpene lactone derived from Centipeda minima (L.) A.Br. (C. minima), a TCM herb, specifically against lung cancer. However, the underlying mechanisms of its effects remain elusive. This study employs network pharmacology and experimental analyses to unravel the molecular mechanisms of Brevilin A in lung cancer. METHODS: The Batman-TCM, Swiss Target Prediction, Pharmmapper, SuperPred, and BindingDB databases were screened to identify Brevilin A targets. Lung cancer-related targets were sourced from GEO, Genecards, OMIM, TTD, and Drugbank databases. Utilizing Cytoscape software, a protein-protein interaction (PPI) network was established. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis (GSEA), and gene-pathway correlation analysis were conducted using R software. To validate network pharmacology results, molecular docking, molecular dynamics simulations, and in vitro experiments were performed. RESULTS: We identified 599 Brevilin A-associated targets and 3864 lung cancer-related targets, with 155 overlapping genes considered as candidate targets for Brevilin A against lung cancer. The PPI network highlighted STAT3, TNF, HIF1A, PTEN, ESR1, and MTOR as potential therapeutic targets. GO and KEGG analyses revealed 2893 enriched GO terms and 157 enriched KEGG pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. GSEA demonstrated a close association between hub genes and lung cancer. Gene-pathway correlation analysis indicated significant associations between hub genes and the cellular response to hypoxia pathway. Molecular docking and dynamics simulations confirmed Brevilin A's interaction with PTEN and HIF1A, respectively. In vitro experiments demonstrated Brevilin A-induced dose- and time-dependent cell death in A549 cells. Notably, Brevilin A treatment significantly reduced HIF-1α mRNA expression while increasing PTEN mRNA levels. CONCLUSIONS: This study demonstrates that Brevilin A exerts anti-cancer effects in treating lung cancer through a multi-target and multi-pathway manner, with the HIF pathway potentially being involved. These results lay a theoretical foundation for the prospective clinical application of Brevilin A.

Discovery of Aurovertin B as a Potent Metastasis Inhibitor against Triple-Negative Breast Cancer: Elucidating the Complex Role of the ATF3-DUSP1 Axis.

Triple-negative breast cancer (TNBC) is characterized by high mortality rates primarily due to its propensity for metastasis. Addressing this challenge necessitates the development of effective antimetastatic therapies. This study aimed to identify natural compounds with potential antimetastatic properties mainly based on the high-throughput phenotypic screening system. This system, utilizing luciferase reporter gene assays combined with scratch wound assays, evaluates compounds based on their influence on the epithelial-mesenchymal transition (EMT) marker E-cadherin. Through this approach, aurovertin B (AVB) was revealed to have significant antimetastatic capability. Notably, AVB exhibited substantial metastasis suppression in many TNBC cell lines, including MDA-MB-231, HCC1937 and 4T1. Also, its remarkable antimetastatic activity was demonstrated in vivo via the orthotopic breast cancer mouse model. Further exploration revealed a pronounced association between AVB-induced upregulation of DUSP1 (dual-specificity phosphatase 1) and its inhibitory effect on TNBC metastasis. Additionally, microarray analysis conducted to elucidate the underlying mechanism of the AVB-DUSP1 interaction identified ATF3 (activating transcription factor 3) as a critical transcription factor instrumental in DUSP1 transcriptional activation. This discovery, coupled with observations of enhanced ATF3-DUSP1 expression and consequent reduction in TNBC metastatic foci in response to AVB, provides novel insights into the molecular mechanisms driving metastasis in TNBC. Significance Statement We construct a high-throughput phenotypic screening system utilizing EMT marker E-cadherin promoter luciferase reporter gene combined with scratch wound assays. Aurovertin B was revealed to possess significant antimetastatic activity through this approach, which was further demonstrated via in vivo and in vitro experiments. The discovery of the regulatory role of the ATF3-DUSP1 pathway enriches our understanding of TNBC metastasis mechanism and suggests the potential of ATF3 and DUSP1 as biomarkers for diagnosing TNBC metastasis.

Pomiferin targeting SLC9A9 based on histone acetylation modification pattern is a potential therapeutical option for gastric cancer with high malignancy.

Changes in histone acetylation status are associated with gastric cancer (GC) progression. Pomiferin is a natural flavonoid, however, the specific role of pomiferin in the treatment of GC is still unclear, and its targets are not well clarified. In this work, the prognostic genes related with histone acetylation in GC were screened by univariate Cox analysis. Next, a risk model of was constructed using least absolute shrinkage and selection operator-Cox regression analyses, and multivariate Cox analysis was used for identifying the independent risk factor. Molecular docking was performed using AutoDock Vina to validate the interaction between solute carrier family 9 member A9 (SLC9A9) and pomiferin. In vitro and in vivo models were applied to investigate the tumor-suppressive role of pomiferin against GC. The inhibitory effects of pomiferin on EGFR/PI3K/AKT signaling were valdiated by Western blotting, immunofluorescence staining and qPCR. Here, a prognostic risk model based on histone acetylation regulators was established, and SLC9A9 was identified as a risk factor associated with histone acetylation status in GC. SLC9A9 expression was associated with abnormal immune microenvironment of tumor. Pomiferin had a high binding affinity with SLC9A9, and both pomiferin treatment and depletion of SLC9A9 repressed the malignant phenotypes of GC cells. Mechanistically, pomiferin inactivates EGFR/PI3K/AKT signaling in GC cells. In summary, SLC9A9, as a indicator of abnormal histone acetylation status of GC, functions as an oncogenic factor. Pomiferin binds with SLC9A9 to inactivate EGFR/PI3K/AKT pathway, to block GC progression, suggesting it is a promising drug for the patients with highly malignant GC.

Neural circuits expressing the serotonin 2C receptor regulate memory in mice and humans.

Declined memory is a hallmark of Alzheimer's disease (AD). Experiments in rodents and human postmortem studies suggest that serotonin (5-hydroxytryptamine, 5-HT) plays a role in memory, but the underlying mechanisms are unknown. Here, we investigate the role of 5-HT 2C receptor (5-HT2CR) in regulating memory. Transgenic mice expressing a humanized HTR2C mutation exhibit impaired plasticity of hippocampal ventral CA1 (vCA1) neurons and reduced memory. Further, 5-HT neurons project to and synapse onto vCA1 neurons. Disruption of 5-HT synthesis in vCA1-projecting neurons or deletion of 5-HT2CRs in the vCA1 impairs neural plasticity and memory. We show that a selective 5-HT2CR agonist, lorcaserin, improves synaptic plasticity and memory in an AD mouse model. Cumulatively, we demonstrate that hippocampal 5-HT2CR signaling regulates memory, which may inform the use of 5-HT2CR agonists in the treatment of dementia.

How to Prevent Nerve Root Injury in Uniportal Full Endoscopic Lumbar Fusion Surgery? Insights from a Cadaveric Anatomical Study with Simulation Surgery.

STUDY DESIGN: The study included two fresh-frozen cadavers. OBJECTIVE: To elucidate the positional relationship between surgical instruments and nerve roots during full endoscopic facet-sparing (FE fs-TLIF) and facet-resecting (FE fr-TLIF) lumbar interbody fusion and propose safe instrumentation insertion procedures and recommend cage glider designs aimed at protecting nerve roots. SUMMARY OF BACKGROUND DATA: Endoscopic surgical techniques are increasingly used for minimally invasive lumbar fusion surgery with FE fr-TLIF and FE fs-TLIF being common approaches. However, the risk of nerve root injury remains a significant concern during these procedures. METHODS: Eight experienced endoscopic spine surgeons performed uniportal FE fr-TLIF and FE fs-TLIF on cadaveric lumbar spines, totaling 16 surgeries. Post-operation, soft tissues were removed to assess the positional relationship between the cage entry point and nerve roots. Distances between the cage entry point, traversing nerve root, and exiting nerve root were measured. Safe instrumentation design and insertion procedures were determined. RESULTS: In FE fr-TLIF, the mean distance between the cage entry point and traversing nerve root was significantly shorter compared to FE fs-TLIF (3.30±1.35 mm vs. 8.58±2.47 mm, respectively; P<0.0001). Conversely, the mean distance between the cage entry point and the exiting nerve root was significantly shorter in FE fs-TLIF compared to FE fr-TLIF (3.73±1.97 mm vs. 6.90±1.36 mm, respectively; P<0.0001). For FE fr-TLIF, prioritizing the protection of the traversing root using a two-bevel tip cage glider was crucial. In contrast, for FE fs-TLIF, a single-bevel tip cage glider placed in the caudal location was recommended. CONCLUSION: This study elucidates the anatomical relationship between cage entry points and nerve roots in uniportal endoscopic lumbar fusion surgery. Protection strategies should prioritize the traversing root in FE fr-TLIF and the exiting root in FE fs-TLIF, with corresponding variations in surgical techniques. LEVEL OF EVIDENCE: V.

Atherogenic index of plasma: a new indicator for assessing the short-term mortality of patients with acute decompensated heart failure.

Objective: Arteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between the atherogenic index of plasma (AIP) and the 30-day mortality rate in patients with acute decompensated heart failure (ADHF). Methods: A total of 1,248 ADHF patients recruited from the Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort between 2019 and 2022 were selected for this study. The primary outcome was the 30-day mortality rate. Multivariable Cox regression, restricted cubic splines (RCS), and stratified analyses were utilized to assess the relationship between AIP and the 30-day mortality rate in ADHF patients. Mediation models were employed for exploratory analysis of the roles of inflammation, oxidative stress, and nutrition in the association between AIP and the 30-day mortality rate in ADHF patients. Results: During the 30-day follow-up, 42 (3.37%) of the ADHF patients died. The mortality rates corresponding to the quartiles of AIP were as follows: Q1: 1.28%, Q2: 2.88%, Q3: 2.88%, Q4: 6.41%. The multivariable Cox regression revealed a positive correlation between high AIP and the 30-day mortality rate in ADHF patients [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08-14.28], independent of age, gender, heart failure type, cardiac function classification, and comorbidities. It is important to note that there was a U-shaped curve association between AIP (<0.24) and the 30-day mortality rate before the fourth quartile, with the lowest 30-day mortality risk in ADHF patients around an AIP of -0.1. Furthermore, mediation analysis suggested significant mediating effects of inflammation and nutrition on the 30-day mortality rate in ADHF patients related to AIP, with inflammation accounting for approximately 24.29% and nutrition for about 8.16% of the mediation effect. Conclusion: This retrospective cohort analysis reveals for the first time the association between AIP and the 30-day mortality rate in ADHF patients. According to our findings, maintaining an AIP around -0.1 in ADHF patients could be crucial for improving poor prognoses from a medical perspective. Additionally, for ADHF patients with high AIP, it is important to assess and, if necessary, enhance nutritional support and anti-inflammatory treatment.