Targeting of KOR by famotidine promotes OPC maturation differentiation and CNS remyelination via STAT3 signaling pathway.

This study aims to identify FDA-approved drugs that can target the kappa-opioid receptor (KOR) for the treatment of demyelinating diseases. Demyelinating diseases are characterized by myelin sheath destruction or formation that results in severe neurological dysfunction. Remission of this disease is largely dependent on the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLGs) in demyelinating lesions. KOR is an important regulatory protein and drug target for the treatment of demyelinating diseases. However, no drug targeting KOR has been developed due to the long clinical trials for drug discovery. Here, a structure-based virtual screening was applied to identify drugs targeting KOR among 1843 drugs of FDA-approved drug libraries, and famotidine was screen out by its high affinity cooperation with KOR as well as the clinical safety. We discovered that famotidine directly promoted OPC maturation and remyelination using the complementary in vitro and in vivo models. Administration of famotidine was not only effectively enhanced CNS myelinogenesis, but also promoted remyelination. Mechanically speaking, famotidine promoted myelinogenesis or remyelination through KOR/STAT3 signaling pathway. In general, our study provided evidence of new clinical applicability of famotidine for the treatment of demyelinating diseases for which there is currently no effective therapy.

Mouse kidney transplantation model: Three novel methods. / å°é¼ è‚¾ç§»æ¤æ¨¡åž‹ï¼š3种创新术式（英文）.

OBJECTIVES: The mouse kidney transplantation model presents challenges in terms of surgical difficulty and low success rate, making it difficult to master. This study aims to provide a crucial model for transplantation immunology research by modifying and developing novel techniques for mouse kidney transplantation. METHODS: A total of 57 pairs of mice were used to establish and compare the modified and innovative surgical techniques for mouse kidney transplantation. Three different surgical models were established, including the abdominal suture technique for orthotopic kidney transplantation, the abdominal cuff technique for orthotopic kidney transplantation, and the cervical cuff technique for ectopic kidney transplantation. BALB/c or C57BL/6 male mice, aged 8 to 12 weeks and weighed 20 to 25 g with specified pathogen free-grade were served as the donor mice or the recipient mice. The surgical technique characteristics, key surgical times, complications, and pathological examination in the early postoperative period were summarized and compared. RESULTS: Three different surgical models of mouse kidney transplantation were successfully established. The comparison of warm ischemic time for the 3 groups of mice showed no statistical significance (P=0.510 4). The abdominal suture group had the shortest total operation time of the donor compared with the abdominal cuff group and the cervical cuff group [(18.3±3.6) min vs (26.2±4.7) min and (22.8±2.5) min; both P<0.000 1]. There was a significant difference in cold ischemia time among the 3 groups (all P<0.000 1), with (60.8±4.1) min in the cervical cuff group, (43.3±5.0) min in the abdominal suture group, and (88.8±6.7) min in the abdominal cuff group. Due to different anastomosis methods, the cervical cuff group had the shortest time [(17.6±2.7) min], whereas the abdominal cuff group had the longest time [(38.8±5.4) min]. The total operation time for the recipients showed significant differences (P<0.000 1), with the abdominal suture group having the shortest time [(44.0±6.9) min], followed by the cervical cuff group [(64.1±5.2) min], and the abdominal cuff group [(80.0±6.0) min] being the longest. In the 32 mice of the abdominal suture group, there were 6 with intraoperative bleeding, including 1 arterial intimal injury bleeding and 5 with bleeding after vessel opening. Six mice had ureteral complications, including ureteral bladder anastomotic stenosis, necrosis, and renal pelvis dilation. Two mice had postoperative abdominal infections. In the abdominal cuff group, there was no intraoperative bleeding, but 6 mice showed mild arterial stenosis and 5 showed venous stenosis, 4 arterial injury, 4 arterial thrombosis, and 2 ureteral complications. No postoperative infections occurred in the mice. In the cervical cuff group, no intraoperative bleeding, arterial intimal injury, arterial/venous stenosis, or thrombosis were found in 13 mice. Five mice had ureteral complications, including ureteral necrosis and infection, which were the main complications in the cervical cuff group. The renal function in mice of the 3 groups remained stable 7 days after surgery. Hematoxylin and eosin staining and periodic acid-Schiff staining showed no significant differences in terms of acute rejection among the 3 surgical methods (all P>0.05). CONCLUSIONS: All 3 surgical methods are able to successfully establish mouse kidney transplantation models, with no significant differences observed in the short-term graft survival and acute rejection. The modified abdominal suture technique and abdominal cuff technique have their respective advantages in research applications. The novel cervical cuff technique for ectopic kidney transplantation model is relatively simple to be prepared and causes less trauma to the mice, providing more options for studies involving xenotransplantation, secondary transplantation, and local lymphatic drainage. However, the difficulty in harvesting the donor kidney and the high incidence of ureteral infections need further validation in long-term survival. This study holds important reference value for choosing the type of mouse kidney transplantation model for different research needs.

PHLDA1 contributes to hypoxic ischemic brain injury in neonatal rats via inhibiting FUNDC1-mediated mitophagy.

Hypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis. In the present study we investigated the role of PHLDA1 in HI-induced neuronal injury and further explored the mechanisms underlying PHLDA1-regulated mitophagy in vivo and in vitro. HI model was established in newborn rats by ligation of the left common carotid artery plus exposure to an oxygen-deficient chamber with 8% O2 and 92% N2. In vitro studies were conducted in primary hippocampal neurons subjected to oxygen and glucose deprivation/-reoxygenation (OGD/R). We showed that the expression of PHLDA1 was significantly upregulated in the hippocampus of HI newborn rats and in OGD/R-treated primary neurons. Knockdown of PHLDA1 in neonatal rats via lentiviral vector not only significantly ameliorated HI-induced hippocampal neuronal injury but also markedly improved long-term cognitive function outcomes, whereas overexpression of PHLDA1 in neonatal rats via lentiviral vector aggravated these outcomes. PHLDA1 knockdown in primary neurons significantly reversed the reduction of cell viability and increase in intracellular reactive oxygen species (ROS) levels, and attenuated OGD-induced mitochondrial dysfunction, whereas overexpression of PHLDA1 decreased these parameters. In OGD/R-treated primary hippocampal neurons, we revealed that PHLDA1 knockdown enhanced mitophagy by activating FUNDC1, which was abolished by FUNDC1 knockdown or pretreatment with mitophagy inhibitor Mdivi-1 (25 µM). Notably, pretreatment with Mdivi-1 or the knockdown of FUNDC1 not only increased brain infarct volume, but also abolished the neuroprotective effect of PHLDA1 knockdown in HI newborn rats. Together, these results demonstrate that PHLDA1 contributes to neonatal HI-induced brain injury via inhibition of FUNDC1-mediated neuronal mitophagy.

Investigation of the correlation between platelet antibodies and peripheral blood cytopenia in patients with hepatocellular carcinoma.

The primary triggers that stimulate the body to generate platelet antibodies via immune mechanisms encompass events such as pregnancy, transplantation, and blood transfusion. Interestingly, our findings revealed that a subset of male patients with hepatocellular carcinoma (HCC), despite having no history of transplantation or blood transfusion, has shown positive results in platelet antibody screenings. This hints at the possibility that certain factors, potentially related to the tumor itself or its treatment, may affect antibody production. To delve the causes we initiated this study. We employed a case-control study approach to analyze potential influential factors leading to the positive results via univariate and multivariate regression analysis. We utilized Kendall's tau-b correlation to examine the relationship between the strength of platelet antibodies and peripheral blood cytopenia. Antitumor medication emerged as an independent risk factor for positive results in HCC patients, and the strength of platelet antibodies positively correlated with the severity of anemia and thrombocytopenia. Without history of blood transfusion, transplantation, pregnancy, those HCC patients underwent recent tumor medication therapy are experiencing peripheral erythrocytopenia or thrombocytopenia, for them platelet antibody screenings holds potential clinical value for prevention and treatment of complications like drug-immune-related anemia and/or bleeding.

Achyranthes bidentata polysaccharides improve cyclophosphamide-induced adverse reactions by regulating the balance of cytokines in helper T cells.

The manuscript aimed to study the immune function maintenance effect of Achyranthes bidentata polysaccharides (ABPs). The mice were divided into the control group, cyclophosphamide-induced (CTX) group, and ABPs-treated (ABP) group. The results showed that, compared with the CTX group, ABPs could significantly improve the spleen index and alleviate the pathological changes in immune organs. Ex vivo study of whole spleen cells, the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were increased. The proliferation of lymphocytes and the proportion of CD3+CD4+ Th cells in peripheral blood mononuclear cells were increased. The transcription of GATA-3, Foxp3, and ROR γ t were decreased, while the transcription of T-bet was increased. The transcriptome sequencing analysis showed that the differentially expressed genes (DEGs) caused by ABPs-treated were mostly downregulated in CTX-induced mice. The Th2-related genes were significantly enriched in DEGs, with representative genes, including Il4, II13, Il9, etc., while increasing the expression of immune effector genes simultaneously, including Ccl3, Ccr5, and Il12rb2. It was suggested that ABPs possibly regulated the balance of cytokines in helper T cells to ameliorate the immune function of CTX-induced mice.

High-performance prediction of epilepsy surgical outcomes based on the genetic neural networks and hybrid iEEG marker.

Accurately identification of the seizure onset zone (SOZ) is pivotal for successful surgery in patients with medically refractory epilepsy. The purpose of this study is to improve the performance of model predicting the epilepsy surgery outcomes using genetic neural network (GNN) model based on a hybrid intracranial electroencephalography (iEEG) marker. We extracted 21 SOZ related markers based on iEEG data from 79 epilepsy patients. The least absolute shrinkage and selection operator (LASSO) regression was employed to integrated seven markers, selected after testing in pairs with all 21 biomarkers and 7 machine learning models, into a hybrid marker. Based on the hybrid marker, we devised a GNN model and compared its predictive performance for surgical outcomes with six other mainstream machine-learning models. Compared to the mainstream models, underpinning the GNN with the hybrid iEEG marker resulted in a better prediction of surgical outcomes, showing a significant increase of the prediction accuracy from approximately 87% to 94.3% (P = 0.0412). This study suggests that the hybrid iEEG marker can improve the performance of model predicting the epilepsy surgical outcomes, and validates the effectiveness of the GNN in characterizing and analyzing complex relationships between clinical data variables.

Prolonged oral intake of green tea polyphenols attenuates delirium-like behaviors in mice induced by anesthesia/surgery.

Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.

Suppression of apoptosis impairs phalangeal joint formation in the pathogenesis of brachydactyly type A1.

Apoptosis occurs during development when a separation of tissues is needed. Synovial joint formation is initiated at the presumptive site (interzone) within a cartilage anlagen, with changes in cellular differentiation leading to cavitation and tissue separation. Apoptosis has been detected in phalangeal joints during development, but its role and regulation have not been defined. Here, we use a mouse model of brachydactyly type A1 (BDA1) with an IhhE95K mutation, to show that a missing middle phalangeal bone is due to the failure of the developing joint to cavitate, associated with reduced apoptosis, and a joint is not formed. We showed an intricate relationship between IHH and interacting partners, CDON and GAS1, in the interzone that regulates apoptosis. We propose a model in which CDON/GAS1 may act as dependence receptors in this context. Normally, the IHH level is low at the center of the interzone, enabling the "ligand-free" CDON/GAS1 to activate cell death for cavitation. In BDA1, a high concentration of IHH suppresses apoptosis. Our findings provided new insights into the role of IHH and CDON in joint formation, with relevance to hedgehog signaling in developmental biology and diseases.

Speech decoding using cortical and subcortical electrophysiological signals.

Introduction: Language impairments often result from severe neurological disorders, driving the development of neural prosthetics utilizing electrophysiological signals to restore comprehensible language. Previous decoding efforts primarily focused on signals from the cerebral cortex, neglecting subcortical brain structures' potential contributions to speech decoding in brain-computer interfaces. Methods: In this study, stereotactic electroencephalography (sEEG) was employed to investigate subcortical structures' role in speech decoding. Two native Mandarin Chinese speakers, undergoing sEEG implantation for epilepsy treatment, participated. Participants read Chinese text, with 1-30, 30-70, and 70-150 Hz frequency band powers of sEEG signals extracted as key features. A deep learning model based on long short-term memory assessed the contribution of different brain structures to speech decoding, predicting consonant articulatory place, manner, and tone within single syllable. Results: Cortical signals excelled in articulatory place prediction (86.5% accuracy), while cortical and subcortical signals performed similarly for articulatory manner (51.5% vs. 51.7% accuracy). Subcortical signals provided superior tone prediction (58.3% accuracy). The superior temporal gyrus was consistently relevant in speech decoding for consonants and tone. Combining cortical and subcortical inputs yielded the highest prediction accuracy, especially for tone. Discussion: This study underscores the essential roles of both cortical and subcortical structures in different aspects of speech decoding.

Accuracy and Usability of Smartphone-Based Distance Estimation Approaches for Visual Assistive Technology Development.

Goal: Distance information is highly requested in assistive smartphone Apps by people who are blind or low vision (PBLV). However, current techniques have not been evaluated systematically for accuracy and usability. Methods: We tested five smartphone-based distance-estimation approaches in the image center and periphery at 1-3 meters, including machine learning (CoreML), infrared grid distortion (IR_self), light detection and ranging (LiDAR_back), and augmented reality room-tracking on the front (ARKit_self) and back-facing cameras (ARKit_back). Results: For accuracy in the image center, all approaches had <±2.5 cm average error, except CoreML which had ±5.2-6.2 cm average error at 2-3 meters. In the periphery, all approaches were more inaccurate, with CoreML and IR_self having the highest average errors at ±41 cm and ±32 cm respectively. For usability, CoreML fared favorably with the lowest central processing unit usage, second lowest battery usage, highest field-of-view, and no specialized sensor requirements. Conclusions: We provide key information that helps design reliable smartphone-based visual assistive technologies to enhance the functionality of PBLV.

Distance effect of single atoms on stability of cobalt oxide catalysts for acidic oxygen evolution.

Developing efficient and economical electrocatalysts for acidic oxygen evolution reaction (OER) is essential for proton exchange membrane water electrolyzers (PEMWE). Cobalt oxides are considered promising non-precious OER catalysts due to their high activities. However, the severe dissolution of Co atoms in acid media leads to the collapse of crystal structure, which impedes their application in PEMWE. Here, we report that introducing acid-resistant Ir single atoms into the lattice of spinel cobalt oxides can significantly suppress the Co dissolution and keep them highly stable during the acidic OER process. Combining theoretical and experimental studies, we reveal that the stabilizing effect induced by Ir heteroatoms exhibits a strong dependence on the distance of adjacent Ir single atoms, where the OER stability of cobalt oxides continuously improves with decreasing the distance. When the distance reduces to about 0.6 nm, the spinel cobalt oxides present no obvious degradation over a 60-h stability test for acidic OER, suggesting potential for practical applications.

Galectin-3 is involved in inflammation and fibrosis in arteriogenic erectile dysfunction via the TLR4/MyD88/NF-κB pathway.

Galectin-3 (Gal-3) is a multifunctional protein that has been linked to fibrosis and inflammation in the cardiovascular system. In this study, we examined the impact of Gal-3 on inflammation and fibrosis in patients with arteriogenic erectile dysfunction (A-ED) and the underlying mechanisms involved. To induce arterial injury, we utilized cuffs on the periaqueductal common iliac arteries of Sprague‒Dawley (SD) rats and administered a high-fat diet to co-induce local atherosclerosis. Our results showed that we successfully developed a novel A-ED model that was validated based on histological evidence. In vivo, the vascular lumen of rats subjected to a high-fat diet and cuff placement exhibited significant narrowing, accompanied by the upregulation of Gal-3, Toll-like receptor 4 (TLR4), and myeloid differentiation primary response protein 88 (MyD88) expression in the penile cavernosa. This led to the activation of nuclear factor kappa B 65 (NF-κB-p65), resulting in reduced intracavernosal pressure, endothelial nitric oxide synthase expression, and smooth muscle content, promoting inflammation and fibrosis. However, treatment with Gal-3 inhibitor-modified citrus pectin (MCP) significantly normalized those effects. In vitro, knocking down Gal-3 led to a significant reduction in TLR4, MyD88, and NF-κB-p65 expression in corpus cavernosum smooth muscle cells (CCSMCs), decreasing inflammation levels. In conclusion, inhibiting Gal-3 may improve A-ED by reducing inflammation, endothelial injury, and fibrosis in the penile corpus cavernosum through the TLR4/MyD88/NF-κB pathway. These findings highlight the potential therapeutic target of Gal-3 in A-ED.

A dataset of behavioral measures on Chinese word production in picture naming.

Most studies of language production have been conducted with speakers of alphabetic languages, but relatively little research has examined languages with non-alphabetic scripts, such as Chinese. Moreover, most work on language word production has investigated phonological output processing (i.e., speaking), whereas comparatively little research has focused on orthographic output, such as writing and typing. Work on non-alphabetic languages and/or written production is particularly promising, given that it speaks to universalities vs. specificity in terms of architectures and mechanisms underlying language processing across all world languages and modalities. The current article reports a dataset of word production in Chinese with spoken and written responses, which includes reaction times of 193,851 trials of naming 403 pictures obtained from 667 participants across 23 Chinese word production experiments. All data were collected in the same experimental environment and from participants with relatively homogenous characteristics, using the same protocols and parameters. The dataset enables researchers to explore how Chinese speakers produce spoken and/or written words, and to identify language-specific features underlying word production.

The impact of resident demand on industrial carbon emissions and the transmission path: Evidence from Zhejiang Province.

The industrial sector is the main source of carbon emissions in most developing countries. Little research has been conducted on demand-side factors and how the demand side affects industrial emissions through the supply side. Therefore, this article selects 2004-2019 panel data on Zhejiang Province, and a multiple linear regression model and a multiple mediating effects model are adopted to explore the impact mechanism and relationship between demand and industrial emissions. We find the following: (i) There is a significant positive influence of demand on emissions, and (ii) demand has an indirect inhibitory effect on industrial emissions through factor market distortion and an indirect promoting effect through technological innovation and energy consumption. (iii) There are two chain intermediary paths led by factor market distortion that have a negative impact on industrial emissions and a chain path led by technological innovation that has a positive impact.

Chromosome-level genome provides insight into the evolution and conservation of the threatened goral (Naemorhedus goral).

BACKGROUND: Gorals Naemorhedus resemble both goats and antelopes, which prompts much debate about the intragenus species delimitation and phylogenetic status of the genus Naemorhedus within the subfamily Caprinae. Their evolution is believed to be linked to the uplift of the Qinghai-Tibet Plateau (QTP). To better understand its phylogenetics, the genetic information is worth being resolved. RESULTS: Based on a sample from the eastern margin of QTP, we constructed the first reference genome for Himalayan goral Naemorhedus goral, using PacBio long-read sequencing and Hi-C technology. The 2.59 Gb assembled genome had a contig N50 of 3.70 Mb and scaffold N50 of 106.66 Mb, which anchored onto 28 pseudo chromosomes. A total of 20,145 protein-coding genes were predicted in the assembled genome, of which 99.93% were functionally annotated. Phylogenetically, the goral was closely related to muskox on the mitochondrial genome level and nested into the takin-muskox clade on the genome tree, rather than other so-called goat-antelopes. The cladogenetic event among muskox, takin and goral occurred sequentially during the late Miocene (~ 11 - 5 Mya), when the QTP experienced a third dramatic uplift with consequent profound changes in climate and environment. Several chromosome fusions and translocations were observed between goral and takin/muskox. The expanded gene families in the goral genome were mainly related to the metabolism of drugs and diseases, so as the positive selected genes. The Ne of goral continued to decrease since ~ 1 Mya during the Pleistocene with active glaciations. CONCLUSION: The high-quality goral genome provides insights into the evolution and valuable information for the conservation of this threatened group.

Accelerated Course of Cerebral Adrenoleukodystrophy After Coronavirus Disease 2019 Infection.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can not only infect the respiratory system but also affect the nervous system through the release of inflammatory factors. Our study aimed to investigate the effect of COVID-19 infection on cerebral adrenoleukodystrophy (ALD). METHODS: Changes in the neurological symptoms of cerebral ALD after infection with COVID-19 from January 2022 to February 2023 were retrospectively analyzed. The primary assessment indicator was the Neurologic Function Scale (NFS) score. RESULTS: A total of 17 male patients with cerebral ALD were enrolled, with a median age of 101 months (80 to 151 months). Among them, 11 (11 of 17, 64.7%) developed an exacerbation of neurological symptoms after COVID-19 infection. Two patients with NFS = 0 started presenting with neurological symptoms after infection. Fifteen patients were in the advanced stage (NFS >1 and/or Loes score >9), of which nine did not progress to major functional disabilities (MFDs). Seven of the nine patients (77.8%) experienced an increase in NFS scores, ranging from 1 to 9 points, within two weeks of COVID-19 infection, with four of them experiencing MFDs. For the other six patients who had progressed to MFDs, there was not much room for further degeneration, so the NFS score did not increase after COVID-19 infection. No deaths related to COVID-19 infection occurred. CONCLUSIONS: COVID-19 infection may aggravate neurological symptoms of cerebral ALD, particularly among patients who have not yet progressed to MFDs. Therefore, COVID-19 may accelerate the course of cerebral ALD, so protecting patients from infection is essential for maintaining the stability of the disease.

Medium to long term of self-report outcomes of high tibial osteotomy in advanced age patients.

PURPOSE: This study aimed to investigate the mid- to long-term benefits of high tibial osteotomy in advanced age patients. METHODS: This retrospective study was conducted in our hospital from January 2017 to January 2021 with data prospectively collected, 47 patients with knee osteoarthritis who over 65 years old were included, and a 1:1 propensity score (PS) of patients < 65 years were matched according to gender, body mass index, and side. Patient demographics, intraooperative and postoperative variables, and patient self-reported outcomes were compared. A generalized linear model was used to screen possible risk factors. RESULTS: A total of 94 consecutive patients were included; the average age of advanced age group was 69.47 + 4.26 years and 57.87 + 5.51 years in the younger group. There were no statistically difference in K-L grade, smoke, drink, comorbidity, ASA, blood loss, operative duration, length of stay, surgical site infection, hinge fracture, DVT, and preooperative and postoperative aFTA; significantly statistical difference of the eFI was found between two groups (P < 0.05). Two groups had comparable VAS and MOMAC scores at one year postoperatively (P > 0.05), while the younger group had lower VAS and WOMAC scores than the advanced age group at the end of follow-up (P < 0.05). Generalized linear model showed both age and eFI were associated with WOMAC scores; there was a statistically significant difference in the effect of eFI on WOMAC scores at different ages (P > 0.05). CONCLUSIONS: Compared with younger patients, advanced age patients have similar short-term benefits, but less long-term benefits. We recommend that patients proposed for HTO be discriminated by eFI, and patients with higher scores should be cautiously selected.

Control mechanism of trichloroethylene back diffusion by microstructure in a low permeability zone.

The trailing effect caused by the back diffusion (BD) of contaminants in low-permeability zones (LPZs), which prolongs remediation time and increases remediation costs, has caused widespread concern. In this study, the BD of trichloroethylene (TCE) from the LPZ to the high-permeability zone (HPZ) was determined using flow cell experiments. The anomalous variance in the BD flux of the TCE-spanning 2-4 times the deviation under identical experimental conditions, attracted our attention. To determine the cause of this aberrant behavior, a micro computed tomography (micro-CT) characterization of the flow cell was conducted, which revealed significant microstructural disparities in the LPZ. The study found that the pore connectivity of LPZs determines the efficiency of BD and that LPZs with different porosities have different sensitivities to connectivity. The pore shape complexity indicates the possibility of BD retardation, and remediation is more difficult for these types of LPZs. Changing the structure of LPZs to improve their remediation efficiency may be a new research topic. Notably, correcting the model parameters through microstructural characterization significantly refined the prediction accuracy.

Acupoint catgut embedding attenuates fibromyalgia pain through attenuation of TRPV1 signaling pathway in mouse.

Objectives: Chronic pain is considered as pain lasting for more than three months and has emerged as a global health problem affecting individuals and society. Chronic extensive pain is the main syndrome upsetting individuals with fibromyalgia (FM), accompanied by anxiety, obesity, sleep disturbances, and depression, Transient receptor potential vanilloid 1 (TRPV1) has been reported to transduce inflammatory and pain signals to the brain. Materials and Methods: Acupoint catgut embedding (ACE) is a novel acupuncture technique that provides continuous effects and convenience. ACE was performed at the bilateral ST36 acupoint. Results: We demonstrated similar pain levels among all groups at baseline. After cold stress, chronic mechanical or thermal nociception was induced (D14: mechanical: 1.85 ± 0.13 g; thermal: 4.85 ± 0.26 s) and reversed in ACE-treated mice (D14: mechanical: 3.99 ± 0.16 g; thermal: 7.42 ± 0.45 s) as well as Trpv1-/- group (Day 14, mechanical: 4.25 ± 0.2 g; thermal: 7.91 ± 0.21 s) mice. Inflammatory mediators were augmented in FM individuals and were abridged after ACE management and TRPV1 gene loss. TRPV1 and its linked mediators were increased in the thalamus (THA), somatosensory cortex (SSC), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) in FM mice. The up-regulation of these mediators was diminished in ACE and Trpv1-/- groups. Conclusion: We suggest that chronic pain can be modulated by ACE or Trpv1-/-. ACE-induced analgesia via TRPV1 signaling pathways may be beneficial targets for FM treatment.

Asymmetric Total Synthesis of Pedrolide.

The asymmetric total synthesis of pedrolide (>200 mg) with an unprecedented [5-5-5-6-6-3] hexacyclic core (pedrolane) was achieved. Its unique bicyclo[2.2.1]heptane ring system was efficiently constructed via an enantioselective ene reaction of cyclopentadiene followed by a Wittig reaction, isomerization, and a diastereoselective intramolecular Diels-Alder reaction cascade. The highly oxygenated carane [6-3] ring system was synthesized via a ring-closing metathesis reaction followed by an unusual free carbene cyclopropanation. Furthermore, the 12 contiguous stereocenters of pedrolide were installed diastereoselectively.