Preoperative systemic immune-inflammation index-based nomogram for lung carcinoma following microwave ablation -a real world single center study.

Background: The preoperative inflammatory condition significantly influences the prognosis of malignancies. We aimed to investigate the potential significance of preoperative inflammatory biomarkers in forecasting the long-term results of lung carcinoma after microwave ablation (MWA). Method: This study included patients who received MWA treatment for lung carcinoma from Jan. 2012 to Dec. 2020. We collected demographic, clinical, laboratory, and outcome information. To assess the predictive capacity of inflammatory biomarkers, we utilized the area under the receiver operating characteristic curve (AUC-ROC) and assessed the predictive potential of inflammatory biomarkers in forecasting outcomes through both univariate and multivariate Cox proportional hazard analyses. Results: A total of 354 individuals underwent MWA treatment, of which 265 cases were included in this study, whose average age was 69.1 ± 9.7 years. The AUC values for the Systemic Inflammatory Response Index (SIRI) to overall survival (OS) and disease-free survival (DFS) were 0.796 and 0.716, respectively. The Cox proportional hazards model demonstrated a significant independent association between a high SIRI and a decreased overall survival (hazard ratio [HR]=2.583, P<0.001). Furthermore, a high SIRI independently correlated with a lower DFS (HR=2.391, P<0.001). We developed nomograms utilizing various independent factors to forecast the extended prognosis of patients. These nomograms exhibited AUC of 0.900, 0.849, and 0.862 for predicting 1-year, 3-year, and 5-year OS, respectively. Additionally, the AUC values for predicting 1-year, 3-year, and 5-year DFS were 0.851, 0.873, and 0.883, respectively. Conclusion: SIRI has shown promise as a valuable long-term prognostic indicator for forecasting the outcomes of lung carcinoma patients following MWA.

Tracking moisture contents in the pollution layer on a composite insulator surface using hyperspectral imaging technology.

Electrical insulators used in transmission lines and outdoor substations are exposed to severe environmental pollution, which significantly increases the risk of power system failure, especially when the pollution layer is highly humid due to adverse weather conditions. The focus of this paper is to establish an effective method for assessing the moisture content (MC) in pollution layers as it serves as a crucial indicator for evaluating the risk of failure in insulators. Hyperspectral imaging (HSI) technology with a spectral range of 371.08-1037.89 nm was applied to determine significant changes in reflectance spectral characteristics in insulators during dynamic wetting and drying periods. Partial least squares regression (PLSR) models were utilized to evaluate the data presentation enhancement abilities of spectral transformation models and the data dimensionality reduction abilities of characteristic band selection methods. Furthermore, PLSR models were developed to calculate the MC along the pixel dimension to visually retrieve the dynamic wetting and drying processes of the pollution layer. The R-squared and root-mean-square error (RMSE) results in the cross-verification set and prediction set of the RE-RF(70%)-PLSR model with two characteristic bands with a wavelength of 543.28 nm and 848.01 nm were as follows: RCV2 = 0.9824, RMSECV = 0.0367, RP2 = 0.9818, RMSEP = 0.0369, respectively. This research contributes towards the visualization retrieval of the MC and offers an important technique for analyzing flashover evolution, optimizing insulator design, and preparing coating materials for insulators.

Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice.

Acute kidney injury (AKI) is defined as a rapid decline in renal function, in which persistent kidney dysfunction gradually progresses to chronic kidney disease (CKD) due to the irreversible loss of nephrons and their maladaptive repair. In recent years, the incidence of AKI has been increasing concerning diverse etiologies, including volume depletion, sepsis, nephrotoxicity, muscle injury, and major trauma, in which ischemia-reperfusion injury (IRI) accounts for most episodes. Development of the IRI model in mice is induced by surgical clamping of the renal pedicles, which provides powerful and controllable tools for preclinical models of AKI. Importantly, the IRI model is deployed at different stages of the AKI development, especially in the processes of AKI to CKD. Despite the IRI model being widely practiced in many laboratories, a series of variables still influence the results of this model. Here, we describe the procedure of IRI model development to provide a repeatable and reliable method for researchers to explore the underlying pathogenesis in the development of AKI and the progression of AKI to CKD.

A role for the cerebellum in motor-triggered alleviation of anxiety.

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.

Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.

BACKGROUND: Alamandine is a newly characterized peptide of renin angiotensin system. Our study aims to investigate the osteo-preservative effects of alamandine, explore underlying mechanism and bring a potential preventive strategy for postmenopausal osteoporosis in the future. METHODS: An ovariectomy (OVX)-induced rat osteoporosis model was established for in vivo experiments. Micro-computed tomography and three-point bending test were used to evaluate bone strength. Histological femur slices were processed for immunohistochemistry (IHC). Bone turnover markers and nitric oxide (NO) concentrations in serum were determined with enzyme-linked immunosorbent assay (ELISA). The mouse embryo osteoblast precursor (MC3T3-E1) cells were used for in vitro experiments. The cell viability was analysed with a Cell Counting Kit­8. We performed Alizarin Red S staining and alkaline phosphatase (ALP) activity assay to observe the differentiation status of osteoblasts. Western blotting was adopted to detect the expression of osteogenesis related proteins and AMP-activated protein kinase/endothelial nitric oxide synthase (AMPK/eNOS) in osteoblasts. DAF-FM diacetate was used for semi-quantitation of intracellular NO. RESULTS: In OVX rats, alamandine alleviated osteoporosis and maintained bone strength. The IHC showed alamandine increased osteocalcin and collagen type I α1 (COL1A1) expression. The ELISA revealed alamandine decreased bone turnover markers and restored NO level in serum. In MC3T3-E1 cells, alamandine promoted osteogenic differentiation. Western blotting demonstrated that alamandine upregulated the expression of osteopontin, Runt-related transcription factor 2 and COL1A1. The intracellular NO was also raised by alamandine. Additionally, the activation of AMPK/eNOS axis mediated the effects of alamandine on MC3T3-E1 cells and bone tissue. PD123319 and dorsomorphin could repress the regulating effect of alamandine on bone metabolism. CONCLUSION: Alamandine attenuates ovariectomy-induced osteoporosis by promoting osteogenic differentiation via AMPK/eNOS axis.

Airway management for a patient with tracheobronchomegaly undergoing lobectomy: a case report.

BACKGROUND: Tracheobronchomegaly (TBM) is a rare disorder mainly characterized by dilatation and malacia of the trachea and major bronchi with diverticularization. This will be a great challenge for airway management, especially in thoracic surgery requiring one-lung ventilation. Using a laryngeal mask airway and a modified double-lumen Foley catheter (DFC) as a "blocker" may achieve one-lung ventilation. This is the first report introducing this method in a patient with TBM. CASE PRESENTATION: We present a 64-year-old man with TBM receiving left lower lobectomy. Preoperative chest computed tomography demonstrated a prominent tracheobronchial dilation and deformation with multiple diverticularization. The most commonly used double-lumen tube or bronchial blocker could not match the distorted airways. After general anesthesia induction, a 4# laryngeal mask was inserted, through which the modified DFC was positioned in the left main bronchus with the guidance of a fiberoptic bronchoscope. The DFC balloon was inflated with 10 ml air and lung isolation was achieved without any significant air leak during one-lung or two-lung ventilation. However, the collapse of the non-dependent lung was delayed and finally achieved by low-pressure artificial pneumothorax. The surgery was successful and the patient was extubated soon after the surgery. CONCLUSIONS: Using a laryngeal mask airway with a modified double-lumen Foley catheter acted as a bronchial blocker could be an alternative method to achieve lung isolation.

Identification of Potential Gene Targets for Suppressing Oviposition in Holotrichia parallela Using Comparative Transcriptome Analysis.

Holotrichia parallela is an important plant pest. Comparative feeding experiments showed that the egg production, oviposition duration and survival rate of H. parallela beetles were significantly higher when they fed on elm leaves than when they fed on willow or purpus privet leaves. RNA sequencing was used to determine transcriptomic changes associated with oviposition. Comparative transcriptome analysis revealed that the beetles that fed on elm and willow had a total of 171 genes with differential expression. When the beetles fed on elm and purpus privet, 3568 genes had differential expression. The vitellogenesis, ovarian serine protease, odorant-binding proteins, acyl-CoA synthetase and follicle cell proteins were commonly upregulated genes in elm-fed beetles compared with those fed on willow/purpus privet leaves. The involvement of the follicle cell protein 3C gene in the regulation of oviposition was confirmed using RNA interference. The results provide insights into the molecular mechanisms underlying oviposition in H. parallela feeding on different host plants. This study also describes a method for identifying potentially effective genes for pest control.

Serum granulosa cell-derived TNF-α promotes inflammation and apoptosis of renal tubular cells and PCOS-related kidney injury through NF-κB signaling.

Polycystic ovary syndrome (PCOS) is a disorder with endocrinal and metabolic problems in reproductive aged women. Evidence shows that PCOS is in a high prone trend to develop kidney diseases. In this study, we investigated the mediators responsible for PCOS-related kidney injury. We found that tumor necrosis factor (TNF-α) levels were significantly increased in serum and primary cultured granulosa cells (GCs) from PCOS patients. Serum TNF-α levels were positively correlated with serum testosterone and luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio, suggesting its positive role in the severity of PCOS. Serum TNF-α levels were also positively correlated with the levels of urinary KapU, LamU, α1-MU and ß2-MU, the markers for renal tubular cell-derived proteinuria. We established a PCOS mouse model by resection of the right kidney, followed by daily administration of dihydrotestosterone (DHT, 27.5 µg, i.p.) from D7 for 90 days. We found that TNF-α levels were significantly increased in the ovary and serum of the mice, accompanied by increased renal tubular cell apoptosis, inflammation and fibrosis in kidneys. Furthermore, the receptor of TNF-α, tumor necrosis factor receptor 1 (TNFR1), was significantly upregulated in renal tubular cells. We treated human ovarian granulosa-like tumor cells (KGN) with DHT (1 µg/ml) in vitro, the conditioned medium derived from the granulosa cell culture greatly accelerated apoptotic injury in human proximal tubular epithelial cells (HKC-8), which was blocked after knockdown of TNF-α in KGN cells. Furthermore, knockdown of TNFR1 in renal tubular epithelial cells greatly ameliorated cell injury induced by granulosa cell-derived conditioned medium. These results suggest that serum TNF-α plays a key role in mediating inflammation and apoptosis in renal tubular cells associated with PCOS-related kidney injury.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines, anti-PD-1 and poly I:C.

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines provide a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents may be combined with DC vaccines to further enhance antitumor activity. Here, we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-programmed death-1 (anti-PD-1) and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy, and the patient remained disease-free for 69 months. The patient received DC vaccines loaded with multiple forms of tumor antigens, including mRNA-tumor associated antigens (TAA), mRNA-neoantigens, and hypochlorous acid (HOCl)-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histocompatibility complex (MHC) class I and II antigen presentation. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy-related adverse events were observed during the treatment. Robust antitumor CD4+ and CD8+ T-cell responses were detected. The patient remains free of disease progression. This is the first case report on the combination of the above three agents to treat glioblastoma patients. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient. A large-scale trial to validate these findings is warranted.

Life table study of Spodoptera frugiperda at different wheat stages and the effect of larval population density on wheat yield.

BACKGROUND: Spodoptera frugiperda is an invasive, widespread agricultural pest in China. However, there have been no reports assessing feeding damage on wheat caused by S. frugiperda. To clarify the fitness and potential damage of S. frugiperda to wheat, this study analyzed the population parameters of S. frugiperda fed on wheat in a laboratory and simulated the potential damage in field conditions. RESULTS: The population parameters of S. frugiperda were compared using life tables on wheat at the seedling and adult plant stages. The adult female longevity of S. frugiperda varied from 12.29 days on seedling plants to 16.60 days on adult plants. Egg production was significantly higher when fed on wheat at the seedling stage (646.34 eggs) than when fed on adult plants (495.86 eggs). On wheat at the seedling and adult plant stages, the mean generation times were 35.42 and 38.34 days, respectively, and the intrinsic rates of increase were 0.15 and 0.14, respectively. Spodoptera frugiperda completed development and increased its population in wheat at both plant growth stages. In the field, the effect of different larval densities on the 1000-kernel weight of wheat was significantly different. An action threshold of 40 larvae per m2 was estimated, and the higher population densities caused a yield loss of 17.7%. CONCLUSION: Spodoptera frugiperda can complete its life cycle on wheat at different stages. Wheat can serve as an alternative host for S. frugiperda. If S. frugiperda reaches 320 larvae per m2 density during wheat growth, it will cause yield loss exceeding 17%. © 2023 Society of Chemical Industry.

Effect of Jiawei Tongqiao Huoxue decoction in basilar artery dolichoectasia mice through yes-associated protein/transcriptional co-activator with PDZ-binding motif pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Jiawei Tongqiao Huoxue decoction (JTHD), composed of Acorus calamus var. angustatus Besser, Paeonia lactiflora Pall., Conioselinum anthriscoides 'Chuanxiong', Prunus persica (L.) Batsch, Ziziphus jujuba Mill., Carthamus tinctorius L., Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep, Zingiber officinale Roscoe, Leiurus quinquestriatus, and Moschus berezovskii Flerov, was developed based on Tongqiao Huoxue decoction in Wang Qingren's "Yilin Gaicuo" in the Qing Dynasty. It has the effect of improving not only the blood flow velocity of vertebral and basilar arteries but also the blood flow parameters and wall shear stress. Especially in recent years, the potential efficacy of traditional Chinese medicine (TCM) for the treatment of basilar artery dolichoectasia (BAD) has attracted great attention as there are still no specific remedies for this disease. However, its molecular mechanism has not been elucidated. To identify the potential mechanisms of JTHD will help to intervene BAD and provide a reference for its clinical application. AIM OF THE STUDY: This study aims to establish a mouse model of BAD and explore the mechanism of JTHD regulating yes-associated protein/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) pathway for attenuating BAD mice development. MATERIALS AND METHODS: Sixty post-modeling C57/BL6 female mice were randomly divided into sham-operated, model, atorvastatin calcium tablet, low-dose JTHD, and high-dose JTHD groups. After 14 days of modeling, the pharmacological intervention was given for 2 months. Then, JTHD was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). ELISA was utilized to detect the changes in vascular endothelial growth factor (VEGF) and lipoprotein a (Lp-a) in serum. EVG staining was conducted to observe the pathological changes of blood vessels. TUNEL method was employed to detect the apoptosis rate of vascular smooth muscle cells (VSMCs). Micro-CT and ImagePro Plus software were used to observe and calculate the tortuosity index, lengthening index, percentage increase in vessel diameter, and tortuosity of the basilar artery vessels in mice. Western blot analysis was performed to detect the expression levels of YAP and TAZ proteins in the vascular tissues of mice. RESULTS: Many effective compounds such as choline, tryptophan, and leucine with anti-inflammation and vascular remodeling were identified in the Chinese medicine formula by LC-MS analysis. The serum levels of VEGF in the model mice decreased significantly while the levels of Lp-a increased obviously compared with those in the sham-operated group. The intima-media of the basilar artery wall showed severe disruption of the internal elastic layer, atrophy of the muscular layer, and hyaline changes of the connective tissue. Apoptosis of VSMCs added. Dilatation, elongation, and tortuosity of the basilar artery became notable, and tortuosity index, lengthening index, percentage increase in vessel diameter, and bending angle remarkably improved. The expression levels of YAP and TAZ protein in blood vessels elevated conspicuously (P < 0.05, P < 0.01). JTHD group markedly reduced the lengthening, bending angle, percentage increase in vessel diameter, and tortuosity index of basilar artery compared with the model group after 2 months of pharmacological intervention. The group also decreased the secretion of Lp-a and increased the content of VEGF. It inhibited the destruction of the internal elastic layer, muscular atrophy, and hyaline degeneration of connective tissue in basilar artery wall. The apoptosis of VSMCs was decreased, and the expression levels of YAP and TAZ proteins were abated (P < 0.05, P < 0.01). CONCLUSIONS: The mechanism of inhibition of basilar artery elongation, dilation, and tortuosity by JTHD, which has various anti-BAD effective compound components, may be related to the reduction in VSMCs apoptosis and downregulation of YAP/TAZ pathway expression.

Preoperative controlling nutritional status score (CONUT) predicts postoperative complications of patients with bronchiectasis after lung resections.

Background: The Controlled Nutritional Status (CONUT) score is a valid scoring system for assessing nutritional status and has been shown to correlate with clinical outcomes in many surgical procedures; however, no studies have reported a correlation between postoperative complications of bronchiectasis and the preoperative CONUT score. This study aimed to evaluate the value of the CONUT score in predicting postoperative complications in patients with bronchiectasis. Methods: We retrospectively analyzed patients with localized bronchiectasis who underwent lung resection at our hospital between April 2012 and November 2021. The optimal nutritional scoring system was determined by receiver operating characteristic (ROC) curves and incorporated into multivariate logistic regression. Finally, independent risk factors for postoperative complications were determined by univariate and multivariate logistic regression analyses. Results: A total of 240 patients with bronchiectasis were included, including 101 males and 139 females, with an average age of 49.83 ± 13.23 years. Postoperative complications occurred in 59 patients (24.6%). The incidence of complications, postoperative hospital stay and drainage tube indwelling time were significantly higher in the high CONUT group than in the low CONUT group. After adjusting for sex, BMI, smoking history, lung function, extent of resection, intraoperative blood loss, surgical approach and operation time, multivariate analysis showed that the CONUT score remained an independent risk factor for postoperative complications after bronchiectasis. Conclusions: The preoperative CONUT score is an independent predictor of postoperative complications in patients with localized bronchiectasis.

Trends in operating room-based glaucoma procedures at a single eye center from 2016-2020.

AIM: To evaluate trends in glaucoma procedures at the Peking University Eye Center in 2016-2020. METHODS: A retrospective search of all glaucoma procedures performed at our institution were performed. Data were analyzed by calculating the absolute numbers and relative weightage of each procedure per year. RESULTS: The average age of glaucoma patients undergoing surgical procedures was 62.33±17.87y, and 55% were women. From 2016 to 2019, the number of surgical procedures performed in glaucoma patients showed an overall upward trend from 749 to 1460, although it decreased slightly in 2020 (n=1393), probably due to the COVID-19 pandemic. The number of trabeculectomies did not change significantly in 2016 (n=161) to 2018 (n=164) but decreased in 2019 (n=139) to 2020 (n=121), indicating a reduction in its relative weightage among glaucoma procedures (from 21.50% to 8.69%). The number of glaucoma drainage device implantations and minimally invasive glaucoma surgeries both increased (50 and 58 respectively in 2019), except in 2020. The number of transscleral cyclophotocoagulation procedures was relatively stable, increasing until 2017 (n=218) and then decreasing. Cataract surgeries with or without glaucoma procedures accounted for a large number of the total surgeries, increasing from 247 (32.97%) in 2016 to 967 (69.42%), among which cataract extraction combined with goniosynechialysis was the most frequent. CONCLUSION: The overall increase in the number of operating room-based surgical procedures is significant. Trabeculectomy is one of the most commonly performed procedures, despite the relative decline in its weightage. Other procedures, including use of glaucoma drainage devices and mini shunts and minimally invasive glaucoma surgeries, are gaining greater acceptance. Notably, lens-related surgery plays an important role in glaucoma management.

Meplazumab in hospitalized adults with severe COVID-19 (DEFLECT): a multicenter, seamless phase 2/3, randomized, third-party double-blind clinical trial.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile.

Passive immunization inhibits tau phosphorylation and improves recognition learning and memory in 3xTg-AD mice.

Tau pathology is essential in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Tau immunotherapy aimed at reducing the progression of tau pathology provides a potential therapeutic strategy for treating these diseases. By screening monoclonal antibodies 43D, 63B, 39E10, and 77G7 that recognize epitopes ranging from tau's N-terminus to C-terminus, we found the 77G7, which targets the microtubule-binding domain promoted tau clearance in a dose-dependent manner by entering neuronal cells in vitro. Intra-cerebroventricular injection of 77G7 antibody reduced tau levels in the wild-type FVB mouse brain. Without influencing the levels of detergent-insoluble and aggregated tau, intravenous injection of 77G7 reduced tau hyperphosphorylation in the brain and improved novel object recognition but not spatial learning and memory in 15-18-month-old 3xTg-AD mice. These studies suggest that epitopes recognized by tau antibodies are crucial for the efficacy of immunotherapy. Immunization with antibody 77G7 provides a novel potential opportunity for tau-directed immunotherapy of AD and related tauopathies.

Modular synthesis of the pheromone (2S,7S)-2,7-nonanediyl dibutyrate and its racemate and their field efficacy to control orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae).

BACKGROUND: Sudden outbreaks of the orange wheat blossom midge, Sitodiplosis mosellana (Géhin) cause huge wheat yield losses. Use of sex pheromones is more efficient than laborious egg counting to monitor these hidden-concealed insects. Quick synthesis of the sex pheromones is therefore required to meet the sudden outbreak needs. RESULTS: A synthetic approach of stereospecific and racemic S. mosellana pheromones was presented. This method afforded the stereospecific and racemic S. mosellana pheromones in three steps and high enantioselectivity (> 98% ee for (2S,7S)-2,7-nonanediyl dibutyrate) in less than 1 day with 74% and 73% overall yields, respectively, whereas most conventional methods require longer synthesis time with less than 40% yield. The synthesis routes could quickly and economically afford the pheromones, starting from synthon (S)-but-3-yn-2-ol (1a) or but-3-yn-2-ol (1b), through the same three-step processes of coupling, reduction, and esterification. The Y-tube olfactometer results showed significant attractiveness of the synthetic stereospecific and racemic sex pheromones to S. mosellana males relative to the blank control (P < 0.001). Field trials also demonstrated significant attractiveness of the synthetic stereospecific and racemic sex pheromones relative to the blank control (P < 0.001). CONCLUSION: This modular approach is conducive to the deployment of field traps and timely responses to S. mosellana outbreaks and can be a time-saving and cost-effective tool to manage S. mosellana. © 2022 Society of Chemical Industry.

Development of a multi-recombinase polymerase amplification assay for rapid identification of COVID-19, influenza A and B.

The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.

[Mechanism of Puerariae Lobatae Radix against lung cancer by inhibiting histone demethylase LSD1].

Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.

A theoretical study on pseudo Mott phase transition of vanadium dioxide.

The structural phase transition (SPT) and metal-insulator phase transition (MIT) always occur simultaneously upon heating from the low-temperature insulator M1 phase to the high-temperature metal R phase in vanadium dioxide, and it is still unclear which one of Mott correlation and Peierls distortion plays a decisive role in the thermally induced phase transition (PT) since 1959. Our density functional theory (DFT)-based calculations revealed that the intermediate phase in the PT, the so-called monoclinic metal phase, is a zero indirect band gap semimetal (P21/c space group) with a pseudo gap (199 meV). From the M1 phase to the monoclinic metal phase, the band gap decreases gradually to zero, and the bonding lengths between vanadium-vanadium atoms remain nearly constant. The SPT and MIT from the intermediate structure to the R phase occur simultaneously with a sudden change of bonding lengths between vanadium-vanadium atoms, in which electrons can jump down rather than jump up to the conduction band minimum (CBM) from the valence band maximum (VBM) under thermal fluctuation in order to lower the total energy of the system to push forward the occurrence of PT. The electron jumping does not require additional energy from Coulomb repulsion between electrons even though it is always present. This SPT is a typical Peierls PT or a pseudo Mott PT rather than an actual Mott PT in the each of the two stages. Our conclusions provide a new understanding of SPT and MIT in vanadium dioxide that has been debated for more than 80 years.