Increased expression of the kynurenine pathway in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

Angiostrongylus cantonensis is the major cause of eosinophilic meningitis worldwide. The imbalance of neurotoxic and neuroprotective metabolites in the kynurenine pathway (KP) have been suggested to contribute to the pathogenesis of central nervous system (CNS) infection. We hypothesized that KP may also be involved in parasitic eosinophilic meningitis. BALB/c mice were orally infected with 40 A. cantonensis L3, intraperitoneal dexamethasone at a dose of 500 µg/kg/day was administered from the seventh day of infection until the end of the study. The Evans blue method was used to analyze blood-brain barrier (BBB) dysfunction, and indoleamine 2,3-dioxygenase (IDO) proteins levels was measured by Western blot, immunohistochemistry (IHC), and immunofluorescence. Tryptophan and kynurenine concentrations were analyzed by IHC and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of Evans blue, IDO, tryptophan and kynurenine in the different groups of mice were compared using the nonparametric Kruskal-Wallis test. BBB dysfunction was found in mice with eosinophilic meningitis. The administration of dexamethasone significantly decreased the amount of Evans blue. An increased IDO expression was shown in Western blot, IHC and immunofluorescence following 2-3 weeks infection. Increased tryptophan and kynurenine expressions in the brain and cerebrospinal fluid (CSF) were also found in IHC and LC-MS/MS studies. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine. In conclusion, A. cantonensis infection inducing BBB damage, then increased the influx of tryptophan into CSF. The administration of dexamethasone significantly decreased the amount of IDO, tryptophan and kynurenine.

Multi-Omics Analysis Reveals the Distinct Features of Metabolism Pathways Supporting the Fruit Size and Color Variation of Giant Pumpkin.

Pumpkin (Cucurbita maxima) is an important vegetable crop of the Cucurbitaceae plant family. The fruits of pumpkin are often used as directly edible food or raw material for a number of processed foods. In nature, mature pumpkin fruits differ in size, shape, and color. The Atlantic Giant (AG) cultivar has the world's largest fruits and is described as the giant pumpkin. AG is well-known for its large and bright-colored fruits with high ornamental and economic value. At present, there are insufficient studies that have focused on the formation factors of the AG cultivar. To address these knowledge gaps, we performed comparative transcriptome, proteome, and metabolome analysis of fruits from the AG cultivar and a pumpkin with relatively small fruit (Hubbard). The results indicate that up-regulation of gene-encoded expansins contributed to fruit cell expansion, and the increased presence of photoassimilates (stachyose and D-glucose) and jasmonic acid (JA) accumulation worked together in terms of the formation of large fruit in the AG cultivar. Notably, perhaps due to the rapid transport of photoassimilates, abundant stachyose that was not converted into glucose in time was detected in giant pumpkin fruits, implying that a unique mode of assimilate unloading is in existence in the AG cultivar. The potential molecular regulatory network of photoassimilate metabolism closely related to pumpkin fruit expansion was also investigated, finding that three MYB transcription factors, namely CmaCh02G015900, CmaCh01G018100, and CmaCh06G011110, may be involved in metabolic regulation. In addition, neoxanthin (a type of carotenoid) exhibited decreased accumulation that was attributed to the down-regulation of carotenoid biosynthesis genes in AG fruits, which may lead to pigmentation differences between the two pumpkin cultivars. Our current work will provide new insights into the potential formation factors of giant pumpkins for further systematic elucidation.

iJAZ-based approach to engineer lepidopteran pest resistance in multiple crop species.

The fall armyworm (FAW) poses a significant threat to global crop production. Here we showed that overexpression of jasmonate ZIM-domain (JAZ) protein GhJAZ24 confers resistance to cotton bollworm and FAW, while also causing sterility in transgenic cotton by recruiting TOPLESS and histone deacetylase 6. We identified the NGR motif of GhJAZ24 that recognizes and binds the aminopeptidase N receptor, enabling GhJAZ24 to enter cells and disrupt histone deacetylase 3, leading to cell death. To overcome plant sterility associated with GhJAZ24 overexpression, we developed iJAZ (i, induced), an approach involving damage-induced expression and a switch from intracellular to extracellular localization of GhJAZ24. iJAZ transgenic cotton maintained fertility and showed insecticidal activity against cotton bollworm and FAW. In addition, iJAZ transgenic rice, maize and tobacco plants showed insecticidal activity against their lepidopteran pests, resulting in an iJAZ-based approach for generating alternative insecticidal proteins with distinctive mechanisms of action, thus holding immense potential for future crop engineering.

[Discussion and analysis the value of supine median³ nystagmus in the diagnosis and treatment of HC-BPPV].

Objective:To explore the clinical value of supine median³ nystagmus in the accurate diagnosis of horizontal semicircular canal benign paroxysmal positional vertigo（HC-BPPV）. Methods:A total of 187 patients with HC-BPPV admitted to the First Affiliated Hospital of Xi'an Jiaotong University from June 2020 to March 2021 were selected. Among them 42 cases of Cupulolithiasis and 145 cases of Canalithiasis. The nystagmus parameters of patients left and right supine position and supine median³ position were recorded in detail by RART. According to the direction of supine median³ nystagmus, patients were divided into three groups: group A（nystagmus to weak side）, group B（nystagmus to strong side）, group C（negative nystagmus）. The canalith repositioning manoeuvres（CRM） was carried out by utility of an automatic vestibular function diagnosis and therapy system（SRM-IV）. The cure rate of CRM in three groups of HC-BPPV patients was compared, Multivariate logistic regression analysis was performed to analyze the influencing factors of CRM for HC-BPPV. Results:The cure rates of group A, group B and group C were 81.58%, 16.13% and 56.25%, respectively. The difference among the three groups was statistically significant. Then a pairwise comparison of group A, B and C, the difference was statistically significant（χ²A-B=40.294,P<0.001,χ²B-C=14.528, P<0.001,χ²A-C=11.606, P=0.001）; the results of multivariate logistic regression analysis showed that the direction of supine median³ nystagmus and BMI were the influencing factors of CRM for HC-BPPV. Conclusion:The direction, intensity and duration of supine median³ nystagmus play an important role in determining the responsibility semicircular canal of HC-BPPV.

Heterologous expression of taxane genes confers resistance to fall armyworm in Nicotiana benthamiana.

KEY MESSAGE: Taxadiene synthase, taxadiene-5α-hydroxylase, and taxane 13α-hydroxylase genes were introduced into Nicotiana benthamiana, and the improved resistance to lepidoptera pest fall armyworm was reported. Fall armyworm (FAW) is a serious agricultural pest. Genetic engineering techniques have been used to create pest-resistant plant varieties for reducing pest damage. Paclitaxel is a diterpenoid natural metabolite with antineoplastic effects in medicine. However, the effects of taxanes on the growth and development of lepidoptera pests, such as the FAW, are unknown. Here, selected paclitaxel precursor biosynthesis pathway genes, taxadiene synthase, taxane 5α-hydroxylase, and taxane 13α-hydroxylase, were engineered in the heterologous host Nicotiana benthamiana plants. Bioassay experiments showed that the transgenic N. benthamiana plants displayed improved resistance to FAW infestation, with degeneration of gut tissues and induced expression of apoptosis-related genes. Cytotoxicity experiment showed that the paclitaxel precursor, 10-deacetylbaccatin III, is cytotoxic to Sf9 cells, causing cell cycle arrest at the G2/M phase and disorder of the cytoskeleton. Metabolome analysis showed that heterologous expression of taxane genes in N. benthamiana affected the digestive system, steroid hormone and purine metabolism pathways of FAW larvae. In summary, this study provides a candidate approach for FAW control.

Electroacupuncture pretreatment mediates sympathetic nerves to alleviate myocardial ischemia-reperfusion injury via CRH neurons in the paraventricular nucleus of the hypothalamus.

BACKGROUND: Myocardial ischemia-reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia-reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVNCRH neurons. METHODS: Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVNCRH neuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot. RESULTS: Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVNCRH neurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVNCRH neurons can counteract this protective effect. CONCLUSION: EA pretreatment can inhibit PVNCRH neurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

Plant-derived strategies to fight against severe acute respiratory syndrome coronavirus 2.

The coronavirus disease 2019 (COVID-19) pandemic has caused an unprecedented crisis, which has been exacerbated because specific drugs and treatments have not yet been developed. In the post-pandemic era, humans and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will remain in equilibrium for a long time. Therefore, we still need to be vigilant against mutated SARS-CoV-2 variants and other emerging human viruses. Plant-derived products are increasingly important in the fight against the pandemic, but a comprehensive review is lacking. This review describes plant-based strategies centered on key biological processes, such as SARS-CoV-2 transmission, entry, replication, and immune interference. We highlight the mechanisms and effects of these plant-derived products and their feasibility and limitations for the treatment and prevention of COVID-19. The development of emerging technologies is driving plants to become production platforms for various antiviral products, improving their medicinal potential. We believe that plant-based strategies will be an important part of the solutions for future pandemics.

A New Target of Electroacupuncture Pretreatment Mediated Sympathetic Nervous to Improve MIRI: Glutamatergic Neurons in Fastigial Nucleus of the Cerebellum.

Ischemic heart disease is a fatal cardiovascular disease that irreversibly impairs the function of the heart, followed by reperfusion leading to a further increase in infarct size. Clinically, we call it myocardial ischemia-reperfusion injury (MIRI). A growing number of clinical observations and experimental studies have found electroacupuncture (EA) to be effective in alleviating MIRI. This study attempts to investigate whether glutamatergic neurons in fastigial nucleus (FN) of the cerebellum are involved in EA pretreatment to alleviate MIRI via sympathetic nerves, and the potential mechanisms of EA pretreatment process. A MIRI model was established by ligating the coronary artery of the left anterior descending branch of the heart for 30 minutes, followed by 2 hours of reperfusion. Multichannel physiological recordings, electrocardiogram, cardiac ultrasound, chemical genetics, enzyme-linked immunosorbent assay and immunofluorescence staining methods were combined to demonstrate that EA pretreatment inhibited neuronal firing and c-Fos expression in FN of the cerebellum and reduced cardiac sympathetic firing. Meanwhile, EA pretreatment significantly reduced cardiac ejection fraction (EF), shortening fraction (SF), percentage infarct area, decreased myocardial norepinephrine (NE), creatine kinase isoenzyme MB (CK-MB) concentrations, and improved MIRI-induced myocardial tissue morphology. The results were similar to the inhibition of glutamatergic neurons in FN. However, the activation of glutamatergic neurons in FN diminished the aforementioned effects of EA pretreatment. This study revealed that glutamatergic neurons in FN of the cerebellum is involved in EA pretreatment mediated sympathetic nervous and may be a potential mediator for improving MIRI.

[Study on the influence of Barbecure combined with Epley on residual dizziness of horizontal canal benign paroxysmal positional vertigo by SRM-vertigo diagnosis system].

Objective:To investigate the influence of Barbecure combined with Epley on residual dizziness of horizontal canal benign paroxysmal positional vertigo（HC-BPPV） by SRM-vertigo diagnosis system. Methods:A total of 406 patients diagnosed with HC-BPPV from Nov 2021 to Nov 2022 were enrolled by rapid axial roll test and Dix-Hallpike in the department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xi'an Jiaotong University. The patients were divided into two groups by hospital card numbers, in which the numbers that were odd were considered as group A, and the numbers that were even were considered as group B. The group A underwent two circles of Barbecure repositioning procedure by SRM-vertigo diagnosis system, while the group B underwent two circles Barbecure combined with Epley repositioning procedure by SRM-vertigo diagnosis system. The treatment was stopped on the next day when two groups of patients were cured, and those who were not cured will continue treatment with the same method. Results:The cure rate of group A was 83.41%, and the cure rate of group B was 80.51%, the difference between the two groups was not-statistically significant difference（P>0.05）. The rate of residual dizziness of group A was 23.30%, the rate of residual dizziness of group B was 11.46%, the difference between the two groups was statistically significant（P<0.05）. Conclusion:The Barbecure combined with Epley otoliths repositioning maneuver by SRM-vertigo diagnosis system can significantly reduce the rate of residual dizziness after the treatment of HC-BPPV, and improve the quality of life of patients.

Climate change impacts of conventional sewage sludge treatment and disposal.

Sewage sludge (SS) management remains a challenge across the world. We quantified the potential climate change impacts of eight conventional technology configurations (TCs) for SS treatment and disposal by considering four different energy exchanges and using a life cycle assessment (LCA) model that employed uncertainty distributions for 104 model parameters. All TCs showed large climate change loads and savings (net values ranging from 123 to 1148 kg CO2-eq/t TS) when the energy exchange was with a fossil-based energy system, whereas loads and savings were approximately three times lower when the energy exchange was with a renewable energy system. Uncertainty associated with the climate change results was more than 100% with fossil-energy exchange and low TS content of SS but was lower for renewable energy. Landfilling had the greatest climate change impact, while thermal drying with incineration had the highest probability of providing better climate change performance than other TCs. The global sensitivity analysis identified nine critical technological parameters. Many of them can be easily measured for relevant SS and technology levels to improve specific estimates of climate change impact. When all scenarios were optimized to the 20% best cases, thermal drying with incineration outperformed the other TCs. This paper contributes to better quantifying the climate change impacts of different technologies used for sludge treatment given changing energy systems and identifies crucial parameters for further technological development.

Mini-review of inventory data for the dewatering and drying of sewage sludge.

Technological comparison and system modelling of sewage sludge treatment are important in terms of sustainable development and climate change mitigation. Dewatering and drying are important processes for reducing volume for transportation and often a requirement for further sludge treatment. Inventory data on mass transfers and material and energy consumptions are therefore crucial in improving and understanding sludge management systems. Reviewing the scientific literature (2003-2021) revealed 55 and 21 datasets on dewatering and drying of sewage sludge, respectively. The scarcity of data did not allow for identifying detailed relationships between inputs and outputs for the technologies, but the reviewed data can serve as the first port of call when planning sludge management. The average total solid (TS) content obtained was statistically different for mechanical dewatering (MDW), deep dewatering, bio-drying (BDR) and thermal drying (TDR). Loss of volatile solids (VS) during dewatering is barely described, but a substantial VS loss was observed for TDR (8%) and BDR (27%). The use of chemical agents in MDW showed typical values of 5-15 g kg-1 TS. The use of energy is low for MDW (average of 0.12 and 0.26 kWh kg-1 TS for raw and digested sludges, respectively) but substantially higher for TDR (average of 3.8 kWh kg-1 TS). The justified inventory data for sludge dewatering and drying provide essential support to system modelling and technological comparison in future studies, but additional data from full-scale plants on energy consumption and the composition of removed water are strongly requested to improve the inventory.

Review of inventory data for the biological treatment of sewage sludge.

The biological treatment of municipal sewage sludge, including anaerobic digestion and composting, was reviewed with the purpose of establishing inventory data to address all the inputs and outputs related to sludge treatment. We identified 193 scientific papers, resulting in 64 datasets on anaerobic digestion and 35 datasets on composting. For anaerobic digestion, biogas production varied significantly (up to a factor of four) depending on the sludge. A useful correlation was identified between the amount of methane produced and the degradation of volatile solids. According to statistical tests, no significant differences were found in biogas production for mesophilic and thermophilic digesters. In addition, methane content varied significantly, and very few data were available for digestate composition or for energy consumption and recovery. For composting, accurate estimates relating to the degradation of sewage sludge could not be made, since organic bulking materials were part of the final composted product. Data on emissions to air are currently scarce, which points to the need for more published information. The inventory data evaluated herein are useful in the feasibility assessment of the biological treatment of sewage sludge, for comparing technologies, for example in LCA studies and as a basis for evaluating the performance of a specific biological sludge treatment plant. However, a great deal of the reviewed data originated from laboratory and pilot-scale studies, and so there is a need for more complete datasets on the performance of full-scale technologies, in order to establish full inventories and identify differences in technologies and operational conditions.

Mini-review of sewage sludge parameters related to system modelling.

System modelling of sewage sludge (SS) treatment attracts a growing interest for better comparison and optimisation of technologies. However, SS parameters need to be generalised to be used in holistic assessments, since scattered data may inhibit the development and interpretation of system models. A review of the literature on SS parameters relevant to modelling SS treatment systems revealed 208 datasets published in 162 publicly available scientific papers. We treated thickened and dewatered sludge in the same data analysis, but in some cases, this was an incorrect assumption. The compositional data showed significant variations, but most of the data subscribed to a lognormal distribution, albeit with varying levels of significance. On average, the thickened sludge contained 3.3 ± 1.7% total solid (TS), and the dewatered sludge contained 21.0 ± 6.7% TS. For the combined data, the average Ash content was 32.4 ± 11.8% of TS. Other characteristic parameters were the lower heating value (LHV) of 22.1 ± 2.1 MJ kg-1 volatile solid (VS) and the biochemical methane potential (BMP) of 0.25 ± 0.11 m3 CH4 kg-1 VS. Fertiliser-related elements were on average 53.3 ± 9.3% C in VS, 6.8 ± 2.2% N in VS, 6.7 ± 2.4% P in Ash and 1.7 ± 1.3% K in Ash. The data reviewed herein provide a good basis for assessing the generality of individual SS data and for selecting key parameters for modelling SS treatment systems. However, the review reveals a need for the better characterisation of SS in the future.

HDAC3 Knockdown Dysregulates Juvenile Hormone and Apoptosis-Related Genes in Helicoverpa armigera.

Insect development requires genes to be expressed in strict spatiotemporal order. The dynamic regulation of genes involved in insect development is partly orchestrated by the histone acetylation-deacetylation via histone acetyltransferases (HATs) and histone deacetylases (HDACs). Although histone deacetylase 3 (HDAC3) is required for mice during early embryonic development, its functions in Helicoverpa armigera (H. armigera) and its potential to be used as a target of insecticides remain unclear. We treated H. armigera with HDAC3 siRNA and RGFP966, a specific inhibitor, examining how the HDAC3 loss-of-function affects growth and development. HDAC3 siRNA and RGFP966 treatment increased mortality at each growth stage and altered metamorphosis, hampering pupation and causing abnormal wing development, reduced egg production, and reduced hatching rate. We believe that the misregulation of key hormone-related genes leads to abnormal pupa development in HDAC3 knockout insects. RNA-seq analysis identified 2788 differentially expressed genes (≥two-fold change; p ≤ 0.05) between siHDAC3- and siNC-treated larvae. Krüppel homolog 1 (Kr-h1), was differentially expressed in HDAC3 knockdown larvae. Pathway-enrichment analysis revealed the significant enrichment of genes involved in the Hippo, MAPK, and Wnt signaling pathways following HDAC3 knockdown. Histone H3K9 acetylation was increased in H. armigera after siHDAC3 treatment. In conclusion, HDAC3 knockdown dysregulated juvenile hormone (JH)-related and apoptosis-related genes in H. armigera. The results showed that the HDAC3 gene is a potential target for fighting H. armigera.

Curcumin-Loaded Oil-Free Self-Assembled Micelles Inhibit the Influenza A Virus Activity and the Solidification of Curcumin-Loaded Micelles for Pharmaceutical Applications.

Curcumin, a well-known natural lipophilic phenolic compound, plays a vital role in inhibiting the influenza infection. Currently, many kinds of formulations for the enhancement of a water dispersion of curcumin have been developed; however, the anti-influenza abilities of formulated curcumin have been much less investigated. In this study, the optimized self-assembled micelles of RH 40/Tween 80 loaded with curcumin (Cur-M) in an oil-free-based system were spherical with a hydrodynamic size at 13.55 nm ± 0.208 and polydispersity at 0.144 characterized by atomic force microscopy and dynamic light scattering, respectively. Additionally, Cur-M significantly increased the bioactivity/stability of curcumin and effectively inhibited the influenza A virus infection and its replication after viral entry, indicating the alteration of the inhibition mechanisms of curcumin against virus infection via RH 40/Tween 80 micelle formulation. Furthermore, a solid formulation (Cur-SM) of Cur-M was successfully developed by a one-pot physical adsorption method using a small amount of adsorbent and ~50% of curcumin/Cur-M that could be burst released from Cur-SM in 1 h, facilitating the fast-releasing applications. Ultimately, all of the results show that Cur-SM acts as a good nano-formulation of curcumin with improved solubility/dispersity in aqueous solutions and demonstrate new anti-influenza mechanisms of curcumin for pharmaceutical development.

Target of Rapamycin Regulates Photosynthesis and Cell Growth in Auxenochlorella pyrenoidosa.

Auxenochlorella pyrenoidosa is an efficient photosynthetic microalga with autotrophic growth and reproduction, which has the advantages of rich nutrition and high protein content. Target of rapamycin (TOR) is a conserved protein kinase in eukaryotes both structurally and functionally, but little is known about the TOR signalling in Auxenochlorella pyrenoidosa. Here, we found a conserved ApTOR protein in Auxenochlorella pyrenoidosa, and the key components of TOR complex 1 (TORC1) were present, while the components RICTOR and SIN1 of the TORC2 were absent in Auxenochlorella pyrenoidosa. Drug sensitivity experiments showed that AZD8055 could effectively inhibit the growth of Auxenochlorella pyrenoidosa, whereas rapamycin, Torin1 and KU0063794 had no obvious effect on the growth of Auxenochlorella pyrenoidosaa. Transcriptome data results indicated that Auxenochlorella pyrenoidosa TOR (ApTOR) regulates various intracellular metabolism and signaling pathways in Auxenochlorella pyrenoidosa. Most genes related to chloroplast development and photosynthesis were significantly down-regulated under ApTOR inhibition by AZD8055. In addition, ApTOR was involved in regulating protein synthesis and catabolism by multiple metabolic pathways in Auxenochlorella pyrenoidosa. Importantly, the inhibition of ApTOR by AZD8055 disrupted the normal carbon and nitrogen metabolism, protein and fatty acid metabolism, and TCA cycle of Auxenochlorella pyrenoidosa cells, thus inhibiting the growth of Auxenochlorella pyrenoidosa. These RNA-seq results indicated that ApTOR plays important roles in photosynthesis, intracellular metabolism and cell growth, and provided some insights into the function of ApTOR in Auxenochlorella pyrenoidosa.

Assessment of Early Growth Response 1 in Tumor Suppression of Esophageal Squamous Cell Carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is associated with poor survival despite surgical resection, and its pathogenesis has been broadly investigated in the past decade. Early growth response 1 (EGR-1) could involve regulating tumor development in ESCC cells. Methods: An attempt was made to examine the molecular and cellular influence of EGR-1 in esophageal cancer cells by RNA extraction, real-time PCR (qRT-PCR), cell culture, small interfering RNA (siRNA) knockdown, western blot, migration assay, and cell viability assay. One hundred and forty-four samples of ESCC were collected from our hospital and analyzed. Significantly higher EGR-1 expression was noted in tumor-adjacent normal tissue compared with tumor lesions. Results: The univariate analysis showed no significant impacts of EGR-1 expression on patients' survival. However, after adjusting for the pathological stage, patients with EGR-1 expression > 68th percentile had lower risks of cancer-related death. Moreover, knockdown of EGR-1 significantly enhanced cell migration, invasion, and resistance to chemotherapeutic agents in two ESCC cell lines. Conclusions: EGR-1 plays a key role in tumor suppression involving tumor viability suppression and reflects the treatment effect of current chemotherapy for ESCC.

Next Generation Sequencing for Potential Regulated Genes and Micro-RNAs of Early Growth Response-1 in the Esophageal Squamous Cell Carcinoma.

Esophageal cancer has a poor prognosis due to its aggressiveness and low survival rate. In Ease Asia, esophageal squamous cell carcinoma (ESCC) outnumbers esophageal adenocarcinoma (EAC). The ESCC patients still have high mortality despite modern surgical resection and neoadjuvant treatment. Determining patient and outcome prognostic factors is critical in ESCC treatment. In esophageal cancer, early growth response-1 (Egr-1) is a tumor suppressor gene, but the mechanism and associated genes are unknown. The study utilizes RNA interference method, the platform of Next Generation Sequencing (NGS) and bioinformatics analysis to investigate the influences after the Egr-1 gene slicing on the ESCC cells. The heat maps of differentially expressed mRNA and microRNAs were analyzed using the algorithm, Burrows-Wheller Aligner. The study showed that the expression of 51 mRNA and 26 microRNAs have significant changes in ESCC cells after Egr-1 knockdown. The KEGG enrichment analysis linked Egr-1-regulated genes and microRNAs. Egr-1 interactions with these genes and microRNAs may be important in tumor progression. In conclusions, this study provided the transcriptome patterns and relating pathway analysis for Egr-1 knockdown in ESCC cells. The mRNA and microRNAs altered by Egr-1 gene silencing might provide key information in the treatment of ESCC.

Trend of HIV Transmitted Drug Resistance After the Introduction of Single-Tablet Regimens in Southern Taiwan.

Background: The prevalence of transmitted drug resistance (TDR) after the universal implementation of STRs is unknown in Taiwan. Objective: This study aimed to investigate the prevalence of TDR in patients with HIV-1 infection, clarify the risk factors for pol resistance, and compare differences in HIV drug resistance before and after the implementation of STRs in Taiwan. Methods: Adult patients infected with HIV-1 were enrolled in this study from 2013 to 2021. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database edition 9. A logistic regression model was used to analyze the risk factors for pol resistance, and the differences in the prevalence of drug resistance from 2013-2016 to 2017-2021 were compared using the Mann-Whitney U-test. General linear regression was used to analyze temporal changes in the annual proportion of TDR overall and by type of antiretroviral drugs. Results: A total of 369 patients were included. The prevalence rate of pol resistance was 9.8% (36/369). The resistance rates to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 3.3%, 6.9%, 0% and 1.8%, respectively. The patients with hepatitis C infection were more likely to have pol resistance (aHR 5.767, CI 1.232-26.991, p=0.026). The prevalence rate of pol resistance did not decrease after the implementation of STRs as first-line therapy in 2017 (11.2% vs 8.7%, aHR 1.329, CI 0.667-2.645, p=0.480), and no significant temporal changes were shown in the annual proportion of TDR overall or by type of antiretroviral drug. Conclusion: Our findings showed a stable prevalence rate of transmitted drug resistance despite the implementation of STRs as the first-line therapy in June 2016.

High Prevalence of Doravirine Resistance in HIV-1-Infected Patients with Virological Failure to an NNRTI-Based Single-Tablet Regimen.

Purpose: This study aimed to investigate the prevalence of resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-tablet regimen (STR) in Taiwanese patients and clarify the clinical implications of using doravirine in patients who fail NNRTI treatment. Patients and Methods: Taiwanese patients infected with HIV-1 who failed NNRTI-based STR treatment were enrolled in this retrospective cohort study from 2015 to 2020. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug-resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database version 9. Median values of continuous variables were compared between two groups using the Mann-Whitney U-test, and categorical variables were compared using the chi-square test or Fisher's exact test. Results: A total of 107 patients were included, of whom 29 were treatment failure to the initial STRs, and 78 failed treatment after switching to an STR. Seventy-four patients failed treatment with TDF/FTC/EFV (Atripla), 30 with TDF/FTC/RPV (Complera) and 3 with TAF/FTC/RPV (Odefsey). The prevalence rates of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were 76%, 86%, 3% and 2%, respectively. Among the 29 patients failure to the initial STRs, 62% developed doravirine resistance, compared to 64% of the 78 the patients who failed treatment after switching to an STR. There were no significant differences in the prevalence of specific NNRTI or doravirine resistance-associated mutations between these two groups. The patients with K65R mutations were more likely to have NNRTI resistance (p = 0.037) and doravirine resistance (p < 0.001). Conclusion: Our findings showed a high rate of doravirine cross-resistance in patients with NNRTI-based STR treatment failure. Doravirine should be used cautiously as a salvage regimen in patients who fail NNRTI treatment.