Gold-Catalyzed Oxidative Rearrangement Strategy to Yield 2-Hydroxycyclohepta-1,3-diene-1-carbonyl Compounds.

A gold-catalyzed oxidative rearrangement of propargyl alcohols, derived from commercially available cyclohex-2-en-1-ones and alkynes, was successfully developed for the efficient synthesis of seven-membered rings. Thorough investigations were conducted to optimize the reaction conditions and evaluate its compatibility with various functional groups. Additionally, this methodology was applied to the formal total synthesis of guanacastepene A, demonstrating its practical utility in complex natural product synthesis. This versatile and efficient approach opens up new possibilities for the construction of diverse seven-membered ring systems, providing valuable building blocks for further exploration in drug discovery and the synthesis of intricate molecules.

The Correlation between Serum Vitamin D and Total IgE Levels and Chronic Spontaneous Urticaria among Chinese Population: A Retrospective Study.

Objective: This study aims to investigate the relationship between serum vitamin D, total IgE levels and chronic spontaneous urticaria (CSU). Methods: We collected data from 101 patients with chronic spontaneous urticaria (experimental group) and 115 healthy normal subjects (control group) in the same period of physical examination. Results: The results showed that the number of deficient and absolute deficient 25-hydroxyvitamin D in the experimental group was significantly lower than in the control group (P < 0.05). Pearson correlation analysis showed that the activity score of CSU patients was negatively correlated with serum vitamin D (r = -0.2278, P = 0.0220) and positively correlated with IgE (r = 0.2078, P = 0.0380). It was observed that serum vitamin D in CSU patients was negatively correlated with their activity (r = -0.2278, P = 0.0220) and positively correlated with age (r = 0.2675, P = 0.0069). The Point-biserial correlation analysis revealed that gender was positively correlated with serum vitamin D (Pearson correlation coefficient = 0.286, P = 0.004) and UAS score (Pearson correlation coefficient = 0.273, P = 0.006). Ordinal logistic regression analysis showed that only serum vitamin D was correlated to activity scores (P = 0.008). In addition to activity scores, age (P = 0.005) and gender (P = 0.04) were correlated to serum vitamin D. Conclusion: The activity score of CSU patients was negatively correlated with serum vitamin D and positively correlated with IgE. Serum vitamin D in CSU patients was negatively correlated with activity score and disease duration and positively correlated with age and gender.

Diaphorobacter nitroreducens synergize with oxaliplatin to reduce tumor burden in mice with lung adenocarcinoma.

Lung adenocarcinoma (LADC) is the most common lung cancer and the leading cause of cancer-related deaths globally. Accumulating evidence suggests that the gut microbiota regulates the host response to chemotherapeutic drugs and can be targeted to reduce the toxicity of current chemotherapeutic agents. However, the effect of Diaphorobacter nitroreducens synergized with oxaliplatin on the gut microbiota and their impact on LADC have never been explored. This study aimed to evaluate the anti-cancer effects of D. nitroreducens, oxaliplatin, and their combined treatment on tumor growth in tumor-bearing mice. The composition of gut microbiota and the immune infiltration of tumors were evaluated by using 16S rRNA gene high-throughput sequencing and immunofluorescence, respectively. The inhibitory effect of the combination treatment with D. nitroreducens and oxaliplatin was significantly stronger than that of oxaliplatin alone in tumor-bearing mice. Furthermore, we observed that the combination treatment significantly increased the relative abundance of Lactobacillus and Akkermansia in the gut microbiota. Meanwhile, the combination treatment significantly increased the proportions of macrophage but decreased the proportion of regulatory T cells in the LADC tumor tissues of mice. These findings underscored the relationship between D. nitroreducens and the gut microbiota-immune cell-LADC axis, highlighting potential therapeutic avenues for LADC treatment. IMPORTANCE: Oxaliplatin is widely used as an effective chemotherapeutic agent in cancer treatment, but its side effects and response rate still need to be improved. Conventional probiotics potentially benefit cancer chemotherapy by regulating gut microbiota and tumor immune infiltration. This study was novel in reporting a more significant inhibitory effect of Diaphorobacter nitroreducens on lung adenocarcinoma (LADC) cells compared with common traditional probiotics and validating its potential as an adjuvant therapy for LADC chemotherapy in mice. This study investigated the impact of D. nitroreducens combined with oxaliplatin on the gut microbiota and immune infiltration of tumors as a potential mechanism to improve anticancer effects.

A Porous Carbazolic Al-MOF for Efficient Aerobic Photo-Oxidation of Sulfides into Sulfoxides under Air.

A robust, microporous, and photoactive aluminum-based metal-organic framework (Al-MOF, LCU-600) has been assembled by an in situ-formed [Al3O(CO2)6] trinuclear building unit and a tritopic carbazole ligand. LCU-600 shows a high water stability and permanent porosity for N2 and CO2 adsorption. Notably, the incorporation of photoresponsive carbazole moieties into LCU-600 makes it a highly efficient and recyclable photocatalyst for aerobic photo-oxidation of sulfides into sulfoxides under an air atmosphere at room temperature. Mechanism investigations unveil that photogenerated holes (h+), superoxide radical anion (O2•-), and singlet oxygen (1O2) are critical active spices for the photo-oxidation reaction performed in an air atmosphere.

The role of blood pressure variability indicators combined with cerebral blood flow parameters in predicting intraventricular hemorrhage in very low birth weight preterm infants.

Background: Hemodynamic instability is the main factor responsible for the development of intraventricular hemorrhage (IVH) in premature newborns. Herein, we evaluated the predictive ability of blood pressure variability (BPV) and anterior cerebral artery (ACA) blood flow parameters in IVH in premature infants with gestational age (GA) ≤32 weeks and birth weight (BW) ≤ 1,500 g. Methods: Preterm infants with GA ≤32 weeks and BW ≤ 1,500 g admitted to the neonatal intensive care unit (NICU) of the hospital affiliated to Yangzhou University from January 2020 to January 2023 were selected as the research subjects. All preterm infants were admitted within 1 h after birth, and systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MABP) were monitored at 1-h intervals. The difference between maximum and minimum values (max-min), standard deviation (SD), coefficient of variation (CV), and successive variation (SV) were used as BPV indicators. On the 1st, 3rd, and 7th day after birth, transcranial ultrasound examination was performed to screen for the occurrence of IVH. On the 24 ± 1 h after birth, systolic velocity (Vs), diastolic velocity (Vd), and resistance index (RI) of the ACA were measured simultaneously. Preterm infants were divided into the IVH group and non-IVH group based on the results of transcranial ultrasound examination, and the correlation between BPV indicators, ACA blood flow parameters, and development of IVH was analyzed. Results: A total of 92 premature infants were enrolled, including 49 in the IVH group and 43 in the non-IVH group. There was no statistically significant difference in baseline characteristics such as BW, GA, sex, and perinatal medical history between the two groups of preterm infants (P > 0.05). The SBP SD (OR: 1.480, 95%CI: 1.020-2.147) and ACA-RI (OR: 3.027, 95%CI: 2.769-3.591) were independent risk factors for IVH in premature newborns. The sensitivity and specificity of combined detection of SBP SD and ACA-RI in predicting IVH were 61.2% and 79.1%, respectively. Conclusion: High BPV and ACA-RI are related to IVH in premature infants with GA ≤32 w and BW ≤1,500 g. Combined detection of SBP SD and ACA-RI has a certain predictive effect on early identification of IVH.

Holistically-Attracted Wireframe Parsing: From Supervised to Self-Supervised Learning.

This article presents Holistically-Attracted Wireframe Parsing (HAWP), a method for geometric analysis of 2D images containing wireframes formed by line segments and junctions. HAWP utilizes a parsimonious Holistic Attraction (HAT) field representation that encodes line segments using a closed-form 4D geometric vector field. The proposed HAWP consists of three sequential components empowered by end-to-end and HAT-driven designs: 1) generating a dense set of line segments from HAT fields and endpoint proposals from heatmaps, 2) binding the dense line segments to sparse endpoint proposals to produce initial wireframes, and 3) filtering false positive proposals through a novel endpoint-decoupled line-of-interest aligning (EPD LOIAlign) module that captures the co-occurrence between endpoint proposals and HAT fields for better verification. Thanks to our novel designs, HAWPv2 shows strong performance in fully supervised learning, while HAWPv3 excels in self-supervised learning, achieving superior repeatability scores and efficient training (24 GPU hours on a single GPU). Furthermore, HAWPv3 exhibits a promising potential for wireframe parsing in out-of-distribution images without providing ground truth labels of wireframes.

Broadband sensory networks with locally stored responsivities for neuromorphic machine vision.

As the most promising candidates for the implementation of in-sensor computing, retinomorphic vision sensors can constitute built-in neural networks and directly implement multiply-and-accumulation operations using responsivities as the weights. However, existing retinomorphic vision sensors mainly use a sustained gate bias to maintain the responsivity due to its volatile nature. Here, we propose an ion-induced localized-field strategy to develop retinomorphic vision sensors with nonvolatile tunable responsivity in both positive and negative regimes and construct a broadband and reconfigurable sensory network with locally stored weights to implement in-sensor convolutional processing in spectral range of 400 to 1800 nanometers. In addition to in-sensor computing, this retinomorphic device can implement in-memory computing benefiting from the nonvolatile tunable conductance, and a complete neuromorphic visual system involving front-end in-sensor computing and back-end in-memory computing architectures has been constructed, executing supervised and unsupervised learning tasks as demonstrations. This work paves the way for the development of high-speed and low-power neuromorphic machine vision for time-critical and data-intensive applications.

Summary of the Experiences and Results of Transesophageal Ultrasound-Guided Ventricular Septal Defect and Atrial Septal Defect Closure Operation.

BACKGROUND: Ventricular septal defect (VSD) and atrial septal defect (ASD) are congenital heart diseases. The techniques of transthoracic closure (TC) and percutaneous closure (PC) for the treatment of VSD and ASD have continuously improved and matured. This study aimed to retrospectively analyze the therapeutic effects of TC and PC on VSD and ASD patients. METHODS: We retrospectively reviewed 928 patients (552 VSD and 376 ASD) who had undergone TC or PC guided by transesophageal ultrasound at the Department of Cardiac Macrovascular Surgery of the First Affiliated Hospital of Nanchang University between August 2010 and August 2020. We collected and evaluated the clinical data of the patients, including age, gender, weight, inlet and outlet diameters of defect, and the operation results of TC and PC. Descriptive statistics were used to analyze means and standard deviations (SD), and the Chi-square test was used to evaluate the difference between groups. RESULTS: Among the 928 patients who were treated with the closure operation, there were no casualties, with 907 patients (97.7%) showing successful closure. Among the 552 VSD patients who were treated with TC, 540 showed successful close, while 12 cases required extracorporeal circulation after the failure of TC. Among the 376 patients with ASD, 256 patients were treated with TC, of which 251 were successful, and five were failures, including three shedding cases. In addition, among the 120 patients who were treated with PC, 116 were successful, and four were failures, including two shedding cases. Postoperative follow up for patients with successful closure operations demonstrated that the complications of aortic and tricuspid regurgitation, hydro-pericardium, III° atrioventricular block, shedding of closure umbrella, hemolysis, and thrombosis had not occurred. CONCLUSION: Closure operation of VSD and ASD by esophageal ultrasound has the advantages of lower trauma and blood loss, shorter hospital stay, simple operation, fewer postoperative complications, and significant therapeutic efficacy.

Exosome-delivered circSATB2 targets the miR-330-5p/PEAK1 axis to regulate proliferation, migration and invasion of lung cancer cells.

Exosomes can carry various kinds of RNAs to mediate intercellular communication. Circular RNA (circRNA) special AT-rich sequence-binding protein 2 (circSATB2) was identified as an oncogene in lung cancer. This study was performed to explore the association of circSATB2 with exosomes and the regulatory mechanism of circSATB2. Exosomes could transmit circSATB2 into lung cancer cells. Exosomes enhanced cell proliferation, invasion, and migration by carrying circSATB2. Exosomal circSATB2 abrogated the inhibitory effect of short hairpin (sh)-circSATB2 on lung cancer progression. Moreover, circSATB2 promoted tumor growth in vivo via exosomes. CircSATB2 interacted with microRNA-330-5p (miR-330-5p) and miR-330-5p targeted pseudopodium enriched atypical kinase 1 (PEAK1). In addition, circSATB2 affected the PEAK1 level via sponging miR-330-5p in lung cancer cells. All results suggested that exosomal transfer of circSATB2 contributed to the malignant development of lung cancer by acting as a sponge of miR-330-5p to upregulate PEAK1.

Low-voltage ultrafast nonvolatile memory via direct charge injection through a threshold resistive-switching layer.

The explosion in demand for massive data processing and storage requires revolutionary memory technologies featuring ultrahigh speed, ultralong retention, ultrahigh capacity and ultralow energy consumption. Although a breakthrough in ultrafast floating-gate memory has been achieved very recently, it still suffers a high operation voltage (tens of volts) due to the Fowler-Nordheim tunnelling mechanism. It is still a great challenge to realize ultrafast nonvolatile storage with low operation voltage. Here we propose a floating-gate memory with a structure of MoS2/hBN/MoS2/graphdiyne oxide/WSe2, in which a threshold switching layer, graphdiyne oxide, instead of a dielectric blocking layer in conventional floating-gate memories, is used to connect the floating gate and control gate. The volatile threshold switching characteristic of graphdiyne oxide allows the direct charge injection from control gate to floating gate by applying a nanosecond voltage pulse (20 ns) with low magnitude (2 V), and restricts the injected charges in floating gate for a long-term retention (10 years) after the pulse. The high operation speed and low voltage endow the device with an ultralow energy consumption of 10 fJ. These results demonstrate a new strategy to develop next-generation high-speed low-energy nonvolatile memory.

LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma.

Collagen type XI alpha 1 (COL11A1) as an oncogene has been reported in several malignant tumors. Herein, we aimed to explore the function of COL11A1 and its upstream regulators in lung adenocarcinoma (LUAD). COL11A1 expression prognostic significance, gene ontology, Kyoto Encyclopedia of Genes and Genomes, and immune infiltration were explored in LUAD. In vitro experimental measurements were implemented to validate the function of COL11A1 and LINC00665 in LUAD cells. Our study demonstrated that LINC00665-2 and COL11A1 were significantly upregulated in LUAD tissues compared with nontumor tissues. COL11A1 was positively correlated with multiple immune cell enrichment, suggesting that COL11A1 may be a prospective therapeutic target to enhance the efficacy of immunotherapy in LUAD. A regulatory mechanism LINC00665-2/microRNAs (miRNAs)/COL11A1 axis was identified to facilitate the tumorigenesis of LUAD. si-LINC00665 transfection induced the inhibition of growth and migration, and apoptosis was reversed by the overexpression of COL11A1 in LUAD cells. In conclusion, LINC00665 as a competing endogenous RNA sponging multiple miRNAs to modulate COL11A1 expression in LUAD, suggesting that LINC00665/miRNAs/COL11A1 axis may contribute to the pathogenesis of LUAD.

Isorhapontigenin Modulates SOX9/TOLLIP Expression to Attenuate Cell Apoptosis and Oxidative Stress in Paraquat-Induced Acute Kidney Injury.

Paraquat (PQ) is a widely used herbicide but can be lethal to humans. The kidney is vital for PQ elimination; therefore, explorations for therapeutic approaches for PQ-induced acute kidney injury (AKI) are of great significance. Here, the effects of a natural bioactive polyphenol isorhapontigenin (ISO) on PQ-AKI were investigated. In vitro experiments carried out in PQ-intoxicated rat renal tubular epithelial cells (NRK-52E) showed that ISO treatment inhibited PQ-induced cell apoptosis and oxidative stress, which was evidenced by the decreased proapoptotic proteins [cleaved caspase 3/9 and poly (ADP-ribose) polymerase (PARP)], the reduced oxidative stress indicators [reactive oxygen species (ROS), malondialdehyde (MDA), and lactate dehydrogenase (LDH) leakage], and the increased antioxidants [superoxide dismutase (SOD), nuclear factor E2-related factor 2 (NRF2), and oxygenase-1 (HO-1)]. Furthermore, 50 mg/kg ISO pretreatment before PQ administration significantly attenuated PQ-AKI in rats, as manifested by the improved renal tubule damage, the reduced serum and urine markers of kidney injury, and the inhibited cell apoptosis and oxidative stress in the renal cortex. Furthermore, expression of sex-determining region Y box 9 (SOX9) and Toll-interacting protein (TOLLIP) in NRK-52E cells and the renal cortex was significantly upregulated after ISO treatment. Overexpression of SOX9 increased TOLLIP transcription and attenuated PQ-induced apoptosis and oxidative stress, whereas knockdown of SOX9 impaired the protective effects of ISO on NRK-52E cells against PQ toxicity. In conclusion, the present study demonstrated that ISO modulated SOX9/TOLLIP expression to attenuate cell apoptosis and oxidative stress in PQ-AKI, suggesting the potential of ISO in treating PQ-poisoned patients.

Clinical application of percutaneous left atrial appendage occlusion guided only by transesophageal echocardiography without fluoroscopy and angiography in the patients with nonvalvular atrial fibrillation.

BACKGROUND AND AIM: The objective of this study was to understand the clinical efficacy and application of the percutaneous left atrial appendage occlusion (PLAAO) guided only by the transesophageal echocardiography (TEE) in patients with nonvalvular atrial fibrillation (NVAF), without using the fluoroscopy and angiography. METHODS: During the time period of this study from June 2020 to June 2021, 32 patients underwent PLAAO and all underwent a TEE guided approach. The anatomical features of the left atrial appendage (LAA) were evaluated and observed by TEE before and during the procedure. LAA occluder device was selected for the appropriate size. Intraoperative TEE guided and monitored the process of PLAAO in real-time, and also evaluated the stability and tightness of the occluder device, following monitored postoperative complications. RESULTS: The PLAAO procedure was successful in all the patients. No serious complications like dislocation of the occluder and embolism were seen. Postoperative TEE demonstrated that the PLAAO occluder devices were in a good position without residual shunting. CONCLUSIONS: PLAAO only guided by TEE may become a safe and reliable surgical procedure, which can protect surgeons and patients from radiation, and can gradually become a novel surgical method of PLAAO with the practical application value.

Presynaptic NMDARs on spinal nociceptor terminals state-dependently modulate synaptic transmission and pain.

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca2+ influx via PreNMDARs. Small conductance Ca2+-activated K+ (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization.

Early physical rehabilitation therapy between 24 and 48 h following acute ischemic stroke onset: a randomized controlled trial.

PURPOSE: Early mobilization is believed to be helpful for patients with acute ischemic stroke. This study aimed to compare the difference between starting rehabilitation between 24 and 48 h and 72 and 96 h following the onset of ischemic stroke. MATERIALS AND METHODS: This was a single-center, single-blind, randomized controlled trial. The early rehabilitation (ER) group started exercising between 24 and 48 h after stroke onset, which the standard rehabilitation (SR) group started exercising between 72 and 96 h. The two groups received sitting, standing, and repetitive body strength training respectively. RESULTS: In this study, 110 patients were analyzed. Patients in the early rehabilitation group had more favorable outcomes (The modified Rankin scale score 0-2, ER group = 32 versus SR group = 20, adjusted odds ratio 2.27, 95% CI 1.05-4.87; p = 0.036) at 3-month follow-up. The simplified Fugl-Meyer assessment (FMA) scores for the lower extremity were influenced by the interaction effect (F = 7.24, p = 0.01). The post-hoc analysis revealed a difference in the lower extremity FMA score at one week after stroke (difference 2.30 (95% CI 0.65-3.96); p = 0.007). CONCLUSIONS: Early physical rehabilitation training between 24 and 48 h may be beneficial and improve patients' lower extremity function within the first week. CLINICAL TRIAL REGISTRATION UNIQUE IDENTIFIER: NCT02718534Implications for rehabilitationAcute ischemic stroke has a variety of symptoms, and acroparalysis is a major concern.Starting physical rehabilitation early can improve the prognosis of patients with ischemic stroke.Early rehabilitation is more conducive to the recovery of lower extremity motor function, but in the subsequent rehabilitation process, the upper extremity function should be paid more attention.

Capn4 aggravates angiotensin II-induced cardiac hypertrophy by activating the IGF-AKT signalling pathway.

Capn4 belongs to a family of calpains that participate in a wide variety of biological functions, but little is known about the role of Capn4 in cardiac disease. Here, we show that the expression of Capn4 was significantly increased in Angiotensin II (Ang II)-treated cardiomyocytes and Ang II-induced cardiac hypertrophic mouse hearts. Importantly, in agreement with the Capn4 expression patterns, the maximal calpain activity measured in heart homogenates was elevated in Ang II-treated mice and oral coadministration of SNJ-1945 (calpain inhibitor) attenuated the total calpain activity measured in vitro. Functional assays indicated that overexpression of Capn4 obviously aggravated Ang II-induced cardiac hypertrophy, whereas Capn4 knockdown resulted in the opposite phenotypes. Further investigation demonstrated that Capn4 maintained the activation of the insulin-like growth factor (IGF)-AKT signalling pathway in cardiomyocytes by increasing c-Jun expression. Mechanistic investigations revealed that Capn4 directly bound and stabilized c-Jun and knockdown of Capn4 increased the ubiquitination level of c-Jun in cardiomyocytes. Additionally, our results demonstrated that the antihypertrophic effect of Capn4 silencing was partially dependent on the inhibition of c-Jun. Overall, these data suggested that Capn4 contributes to cardiac hypertrophy by enhancing the c-Jun-mediated IGF-AKT signalling pathway and could be a potential therapeutic target for hypertrophic cardiomyopathy.

Management of Multiple Skeletal Tuberculosis Wounds Complicated With Multiple Deep Sinus Tracts: A Case Report.

BACKGROUND: Tuberculosis (TB) is a leading infectious disease worldwide. It rarely occurs in the scapula and toe joints and is easily misdiagnosed. Without prompt treatment, the associated lesions can spread to surrounding soft tissues such as joint capsules, muscles, tendons, and fascia. In severe cases, the bones and articular surfaces can become significantly damaged; it is not uncommon for deep skeletal TB wounds with sinus tracts to form, which are very difficult to treat. We report our successful wound care management approach for one patient with multiple skeletal TB complicated with multiple deep sinus tracts. CASE: The patient was treated with anti-TB medications, and wound and bone debridement (sharps, surgical) combined with vacuum-shielded drainage (VSD) (Kula, CG Bio Co Ltd, Gyeonggi-do, South Korea) to fill the sinus tract. We removed the caseous (cheese-like) necrotic tissue, purulent drainage, and necrotic tissue at the base of the wound to ensure optimal wound care. Throughout the course of treatment, we selected different types of dressings to maintain moist wound healing and absorb excessive drainage. After 144 days of treatment, the wound and deep sinus tracts completely healed. CONCLUSIONS: Wounds related to skeletal TB with multiple sinus tracts are difficult to manage and heal. We found our wound protocol that included timely debridement and use of VSD was effective for the management of these complex wounds. Specifically, our approach filled the dead space in the sinus tract, removed excessive drainage, promoted the growth of granulation tissue, and overall promoted tissue healing.

Extracellular matrix protein laminin ß1 regulates pain sensitivity and anxiodepression-like behaviors in mice.

Patients with neuropathic pain often experience comorbid psychiatric disorders. Cellular plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion. However, substantial efforts have thus far been focused on the intracellular mechanisms of plasticity rather than the extracellular alterations that might trigger and facilitate intracellular changes. Laminin, a key element of the extracellular matrix (ECM), consists of one α-, one ß-, and one γ-chain and is implicated in several pathophysiological processes. Here, we showed in mice that laminin ß1 (LAMB1) in the ACC was significantly downregulated upon peripheral neuropathy. Knockdown of LAMB1 in the ACC exacerbated pain sensitivity and induced anxiety and depression. Mechanistic analysis revealed that loss of LAMB1 caused actin dysregulation via interaction with integrin ß1 and the subsequent Src-dependent RhoA/LIMK/cofilin pathway, leading to increased presynaptic transmitter release probability and abnormal postsynaptic spine remodeling, which in turn orchestrated the structural and functional plasticity of pyramidal neurons and eventually resulted in pain hypersensitivity and anxiodepression. This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin ß1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression.

circSNX6 (hsa_circ_0031608) enhances drug resistance of non-small cell lung cancer (NSCLC) via miR-137.

circRNAs have been suggested to modulate NSCLC tumorigenesis and drug resistance. Whether circSNX6 affects NSCLC remains unclear. In this study, we aim to investigate the role of circSNX6 in drug resistance of NSCLC exposed to cisplatin. RT-qPCR method was used to investigate expression levels of circSNX6, miR-137 and CXCL12. MTT, cell colony formation and TUNEL assays were utilized to assess cell viability, proliferation, apoptosis, respectively. Xenograft assay was conducted to examinein vivotumor growth. circSNX6 overexpression caused enhanced cell viability and proliferation of H1299 and Calu-1, while it inhibited apoptosis under cisplatin treatment. miR-137 inhibitor greatly rescued cell viability, proliferation and apoptosis of circSNX6 knockdown H1299 cells. miR-137 mimic increased ROS generation, as well as reduced GSH and SOD levels, whereas miR-137 inhibitor exerted opposing effect. circSNX6 knockdown also enhanced ROS generation, as well as decreased GSH and SOD levels. CXCL12 partially restored miR-137 mimic-modulated cell viability, proliferation and apoptosis. Herein, our group proposes circSNX6 as key regulator for drug resistance of NSCLC. The findings provide solid groundings for understanding of NSCLC pathogenesis and development of therapeutics.

Is flexible bronchoscopy necessary in the preoperative workup of patients with peripheral cT1N0 subsolid lung cancer? -a prospective multi-center cohort study.

BACKGROUND: Necessity of flexible bronchoscopy (FB) examination as a routine preoperative work-up for peripheral clinical T1N0 subsolid lung cancer was unknown. METHODS: This was a prospective, multi-center clinical trial (NCT03591445). Patients with peripheral GGO nodules (GGNs) who were candidates for surgical resection were enrolled. FB examination was performed preoperatively. Surgical plan could be changed if any aberrant histologic and anatomic findings were detected by FB examination. Primary endpoint was the rate that surgical plan was changed by positive FB findings. Secondary endpoints were rate of positive FB findings and rate of procedural complications. RESULTS: Six hundred and fifteen patients with peripheral subsolid nodules detected by thoracic CT were enrolled. There were 187 (30.4%) male and 428 (69.6%) female patients, mean age was 54.85±10.41 y (range, 26-78). 262 (42.6%) patients had pure GGNs and 353 (57.4%) patients had part-solid nodules. Mean size of nodules was 13.87±6.37 mm (range, 5-30). FB examinations confirmed one (0.16%) adenocarcinoma, seven (1.14%) bronchial variations, one (0.16%) segmental bronchostenosis, one (0.16%) segmental bronchial occlusion and one (0.16%) bronchial inflammation. No complications of FB examinations occurred. 568 (92.35%) thoracoscopic and 47 (7.65%) open surgeries were performed. No established surgical plan was changed by positive FB findings. Final pathologies revealed 26 (4.2%) adenocarcinoma in situ (AIS), 240 (39%) minimal invasive adenocarcinomas (MIAs), 343 (55.8%) invasive adenocarcinomas (IADs), one (0.2%) adenosquamous cell carcinoma, one (0.2%) squamous cell carcinoma, two (0.3%) atypical adenoid hyperplasia and two (0.3%) inflammations. CONCLUSIONS: FB examination was unnecessary in the preoperative assessment of peripheral clinical T1N0 subsolid lung cancer.