Allelic heterogeneity of TTNtv dilated cardiomyopathy can be modeled in adult zebrafish.

Allelic heterogeneity (AH) has been noted in truncational TTN-associated (TTNtv-associated) dilated cardiomyopathy (DCM); i.e., mutations affecting A-band-encoding exons are pathogenic, but those affecting Z-disc-encoding exons are likely benign. The lack of an in vivo animal model that recapitulates AH hinders the deciphering of the underlying mechanism. Here, we explored zebrafish as a candidate vertebrate model by phenotyping a collection of zebrafish ttntv alleles. We noted that cardiac function and sarcomere structure were more severely disrupted in ttntv-A than in ttntv-Z homozygous embryos. Consistently, cardiomyopathy-like phenotypes were present in ttntv-A but not ttntv-Z adult heterozygous mutants. The phenotypes observed in ttntv-A alleles were recapitulated in null mutants with the full titin-encoding sequences removed. Defective autophagic flux, largely due to impaired autophagosome-lysosome fusion, was also noted only in ttntv-A but not in ttntv-Z models. Moreover, we found that genetic manipulation of ulk1a restored autophagy flux and rescued cardiac dysfunction in ttntv-A animals. Together, our findings presented adult zebrafish as an in vivo animal model for studying AH in TTNtv DCM, demonstrated TTN loss of function is sufficient to trigger ttntv DCM in zebrafish, and uncovered ulk1a as a potential therapeutic target gene for TTNtv DCM.

Bronchial epithelial transcriptomics and experimental validation reveal asthma severity-related neutrophilc signatures and potential treatments.

Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.

Application of contrast-enhanced ultrasound in diagnosis and grading of bladder urothelial carcinoma.

PURPOSE: To explore the application of contrast-enhanced ultrasound (CEUS) for the diagnosis and grading of bladder urothelial carcinoma (BUC). METHODS: The results of a two-dimensional ultrasound, color Doppler ultrasound and CEUS, were analyzed in 173 bladder lesion cases. The ultrasound and surgical pathology results were compared, and their diagnostic efficacy was analyzed. RESULTS: There were statistically significant differences between BUC and benign lesions in terms of color blood flow distribution intensity and CEUS enhancement intensity (both P < 0.05). The area under the time-intensity curve (AUC), rising slope, and peak intensity of BUC were significantly higher than those of benign lesions (all P < 0.05). The H/T (height H / basal width T)value of 0.63 was the critical value for distinguishing high- and low-grade BUC, had a diagnostic sensitivity of 80.0% and a specificity of 60.0%. CONCLUSION: The combination of CEUS and TIC can help improve the diagnostic accuracy of BUC. There is a statistically significant difference between high- and low-grade BUC in contrast enhancement intensity (P < 0.05); The decrease of H/T value indicates the possible increase of the BUC grade.

A Predictive Nomogram for Intensive Care-Acquired Weakness after Cardiopulmonary Bypass.

PURPOSE: Intensive care unit-acquired weakness (ICUAW) affects patient prognosis after cardiopulmonary bypass (CPB) surgery, but its risk factors remain unclear. We investigated these risk factors and developed a nomogram for predicting ICUAW after CPB. METHODS: Baseline characteristics, preoperative laboratory data, and intra- and postoperative variables of 473 patients after CPB were determined in this prospective cohort study. Lower limb muscles on bedside ultrasound images were compared 1 day before and 7 days after CPB. Risk factors were assessed using logistic regression models. RESULTS: Approximately 50.95% of the patients developed ICUAW after CPB. The body mass index (BMI), New York Heart Association (NYHA) class, lactate, albumin, aortic clamping time, operation time, and acute physiological and chronic health evaluation II were determined as independent risk factors. The average absolute error of coincidence was 0.019; the area under the curve, sensitivity, and specificity were 0.811, 0.727, and 0.733, respectively, for the predictive nomogram. CONCLUSION: A high BMI, poor NYHA class, preoperative high serum lactate, low serum albumin, long surgical duration, aortic clamping, and high acute physiological and chronic health evaluation II score are risk factors for ICUAW after CPB. This robust and easy-to-use nomogram was developed for clinical decision-making.

Prognostic value of obesity in patients with cancer treated with immune checkpoint inhibitors: An updated meta­analysis and systematic review.

Accumulating interest has been surging over the past few years regarding the effects of obesity on immunotherapy. In addition to the body mass index (BMI), imaging-quantified body fat compartments have been investigated. The present study aimed to evaluate the predictive value of the BMI and computed tomography (CT)-based body fat in patients with cancer receiving immunotherapy. For this purpose, the PubMed, MEDLINE, EMBASE and Cochrane databases were searched from January 2017 to July 2022. Clinical studies evaluating the association between BMI or body fat and survival of patients with cancer treated with immune checkpoint inhibitors (ICIs) were included. In total, 15 studies reporting on the BMI were included in the meta-analysis and 16 studies evaluating body fat were included in the systematic review. According to the classification of the World Health Organization, overweight and obese patients with ICI treatment showed improved overall survival [overweight vs. normal: Hazard ratio (HR)=0.79, 95% confidence interval (CI)=0.64-0.98, P=0.03; obese vs. normal: HR=0.75, 95% CI=0.60-0.94, P=0.013] and progression-free survival (overweight vs. normal: HR=0.82, 95% CI=0.70-0.97, P=0.02; obese vs. normal: HR=0.81, 95% CI=0.65-1.02, P=0.07). Among the articles investigating the effect of body fat composition on the efficacy of immunotherapy, a number of studies included various CT analysis techniques and cutoffs to define body fat composition. Associations of body fat with survival were contradictory in different patients with cancer treated with immunotherapy. Obesity was associated with better survival in patients with cancer treated with ICIs. Further analyses are required to demonstrate the prognostic value of body fat in patients with cancer immunotherapy.

Prognostic Value of Body Composition and Systemic Inflammatory Markers in Patients with Locally Advanced Cervical Cancer Following Chemoradiotherapy.

Background: Abnormal changes in body composition and systemic inflammation response have been associated with poor survival of cancer patients. Our study was to explore the prognostic value of the association between body composition indicators and systemic inflammation markers among patients with locally advanced cervical cancer (LACC) who underwent concurrent chemoradiotherapy (CCRT). Methods: We retrospectively reviewed medical records of LACC patients treated between 2016 and 2019. Subcutaneous, visceral and intra-muscular adipose index (SAI, VAI and IMAI) and skeletal muscle index (SMI) were derived from computed tomography (CT). Kaplan-Meier analysis and Univariate and multivariate Cox analyses were used to evaluate the survival. A nomogram was constructed to assess the prognostic value. Results: The study included 196 patients treated with CCRT. According to multivariable Cox analyses, IIIC1r (P = 0.045), high systemic immune-inflammation index (SII) (P = 0.004), sarcopenia (P = 0.008), high SAI (P = 0.016) and high VAI (P = 0.001) were significantly risk factors for overall survival (OS). Kaplan-Meier analysis showed that patients with low lymphocyte-to-monocyte ratio (LMR) and sarcopenia had longer OS than those with high LMR and sarcopenia (P = 0.023). The high neutrophil-to-lymphocyte ratio (NLR) in non-sarcopenic patients showed better survival (P = 0.022). Low VAI (P = 0.019) or low IMAI (P = 0.019) combined with low SII had a favorable OS. Low LMR combined with low SAI was associated with longer OS (P = 0.022). The calibration plots of nomogram predicting the 3-year and 5-year OS rates were close to the ideal models. Conclusion: Inflammation factors were closely associated with abnormal muscle and fat distribution. The combined prognostic value of body composition indicators and systemic inflammation markers was reliable in predicting survival for LACC patients.

A review on edible insects in China: Nutritional supply, environmental benefits, and potential applications.

This review explored the potential of edible insects to address the challenges of malnutrition and food security. Although grain production in China has met the Food and Agriculture Organization standards, the shortage of protein supply is still a big issue. Moreover, expanding livestock farming is considered unsustainable and environmentally unfriendly. Edible insects have become an alternative with higher sustainable and ecological properties. There are 324 species of insects currently consumed in China, and they have high nutritional value, with a rich source of protein and unsaturated fatty acids. Insect farming provides numerous benefits, including green feeds for livestock, poultry, and aquaculture, sustainable organic waste management, as well as industrial and pharmaceutical raw materials. The food toxicological evaluations conducted in China indicated that edible insects are safe for general consumption by the Chinese, but allergies and other related food safety issues should not be ignored. Consumer acceptance is another barrier to overcome, with different schemas between China and Western countries. More research on the potential functions of edible insects and their product development may enhance their acceptance in China. Overall, incorporating edible insects into our diet is a promising solution to address challenges related to protein supply and food security. To ensure safety and sustainability, appropriate legislation, quality regulations, large-scale insect farms, and acceptable processing techniques are necessary. Moreover, more scientific research and social awareness are required to promote the culture and utilization of edible insects in China.

Ferroelectric Nanorods as a Polymer Interface Additive for High-Performance Garnet-Based Solid-State Batteries.

Sandwiching polymer interlayers between the electrode and solid electrolyte is considered promising in solving the interfacial issues arising from solid-solid contact in garnet-based solid-state batteries, but drawbacks including low ionic conductivity, inferior Li+ transference number, and unsatisfying mechanical property of the polymer hindered the practical application of such strategy. To solve the mentioned shortcomings of the polymer interlayer simultaneously, we introduce the ferroelectric material, BaTi2O5 (BT) nanorods, into the polymer matrix in this work. By taking full advantage of the plasticization effect and intrinsic spontaneous polarization of the introduced ferroelectric, the polymer's ionic conductivity and Li+ transference number have been significantly enhanced. The built-in electric field BT introduced also benefits the modulation of CEI components formed on the cathode particles, further enhancing the battery performance by decreasing cathode degradation. Besides, the BT nanorods' particular high aspect ratio also helps increase the mechanical property of the obtained polymer film, making it more resistant to lithium dendrite growth across the interface. Benefitting from the merits mentioned above, the assembled lithium symmetric cells using garnet SE with the BT-modified polymer interlayer exhibit stable cycling performance (no short circuit after 1000 h under RT) with low polarization voltage. The full battery employing LiFePO4 as a cathode also presents superior capacity retentions (94.6% after 200 cycles at 0.1 C and 93.4% after 400 cycles at 0.2 C). This work highlights the importance of ferroelectric materials with specific morphology in enhancing the electrochemical performance of polymer-based electrolytes, promoting the practical application of solid-state batteries.

Kidney transcriptome and cystic kidney disease genes in zebrafish.

Introduction: Polycystic kidney disease (PKD) is a condition where fluid filled cysts form on the kidney which leads to overall renal failure. Zebrafish has been recently adapted to study polycystic kidney disease, because of its powerful embryology and genetics. However, there are concerns on the conservation of this lower vertebrate in modeling polycystic kidney disease. Methods: Here, we aim to assess the molecular conservation of zebrafish by searching homologues polycystic kidney disease genes and carrying transcriptome studies in this animal. Results and Discussion: We found that out of 82 human cystic kidney disease genes, 81 have corresponding zebrafish homologs. While 75 of the genes have a single homologue, only 6 of these genes have two homologs. Comparison of the expression level of the transcripts enabled us to identify one homolog over the other homolog with >70% predominance, which would be prioritized for future experimental studies. Prompted by sexual dimorphism in human and rodent kidneys, we studied transcriptome between different sexes and noted significant differences in male vs. female zebrafish, indicating that sex dimorphism also occurs in zebrafish. Comparison between zebrafish and mouse identified 10% shared genes and 38% shared signaling pathways. String analysis revealed a cluster of genes differentially expressed in male vs. female zebrafish kidneys. In summary, this report demonstrated remarkable molecular conservation, supporting zebrafish as a useful animal model for cystic kidney disease.

Prolonged High-Fat Diet Consumption throughout Adulthood in Mice Induced Neurobehavioral Deterioration via Gut-Brain Axis.

Neuropsychiatric disorders have been one of the worldwide health problems contributing to profound social and economic consequences. It is reported that consumption of an excessive high-fat diet (HFD) in middle age could induce cognitive and emotional dysfunctions, whereas the mechanisms of the effects of long-term HFD intake on brain disorders have not been fully investigated. We propose a hypothesis that prolonged HFD intake throughout adulthood could lead to neurobehavioral deterioration via gut-brain axis. In this study, the adult C57BL/6J mice consuming long-term HFD (24 weeks) exhibited more anxiety-like, depression-like, and disruptive social behaviors and poorer performance in learning and memory than control mice fed with a normal diet (ND). In addition, the homeostasis of gut microbiota was impaired by long-term HFD consumption. Changes in some flora, such as Prevotellaceae_NK3B31_group and Ruminococcus, within the gut communities, were correlated to neurobehavioral alterations. Furthermore, the gut permeability was increased after prolonged HFD intake due to the decreased thickness of the mucus layer and reduced expression of tight junction proteins in the colon. The mRNA levels of genes related to synaptic-plasticity, neuronal development, microglia maturation, and activation in the hippocampus and prefrontal cortex of HFD-fed mice were lower than those in mice fed with ND. Interestingly, the transcripts of genes related to tight junction proteins, ZO-1 and Occludin involved in blood-brain-barrier (BBB), were decreased in both hippocampus and prefrontal cortex after long-term HFD consumption. Those results indicated that chronic consumption of HFD in mice resulted in gut microbiota dysbiosis, which induced decreased expression of mucus and tight junction proteins in the colon, in turn leading to local and systemic inflammation. Those changes could further contribute to the impairment of brain functions and neurobehavioral alterations, including mood, sociability, learning and memory. In short, long-term HFD intake throughout adulthood could induce behavioral phenotypes related to neuropsychiatric disorders via gut-brain axis. The observations of this study provide potential intervention strategies to reduce the risk of HFD via targeting the gut or manipulating gut microbiota.

Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy.

Modifier genes contribute significantly to our understanding of pathophysiology in human diseases; however, effective approaches to identify modifier genes are still lacking. Here, we aim to develop a rapid F0-based genetic assay in adult zebrafish using the bag3 gene knockout (bag3e2/e2) cardiomyopathy model as a paradigm. First, by utilizing a classic genetic breeding approach, we identified dnajb6b as a deleterious modifier gene for bag3 cardiomyopathy. Next, we established an F0-based genetic assay in adult zebrafish through injection of predicted microhomology-mediated end joining (MMEJ)-inducing single guide RNA/Cas9 protein complex. We showed that effective gene knockdown is maintained in F0 adult fish, enabling recapitulation of both salutary modifying effects of the mtor haploinsufficiency and deleterious modifying effects of the dnajb6b gene on bag3 cardiomyopathy. We finally deployed the F0-based genetic assay to screen differentially expressed genes in the bag3 cardiomyopathy model. As a result, myh9b was identified as a novel modifier gene for bag3 cardiomyopathy. Together, these data prove the feasibility of an F0 adult zebrafish-based genetic assay that can be effectively used to discover modifier genes for inherited cardiomyopathy.

Effective immobilization of Cd(II) in soil by biotic zero-valent iron and coexisting sulfate.

In this work, zero-valent iron (ZVI) combined with anaerobic bacteria was used in the remediation of Cd(II)-polluted soil under the mediation of sulfate (SO42-). Owing to hydrogen-autotrophic sulfate reduction, serious corrosion occurred on sulfate-mediated biotic ZVI in terms of solid phase characterization as massive corrosive products (e.g., goethite, magnetite and green rust) were formed, which were crucial in the immobilization of Cd(II). Thus, this integrated system achieved a 4.9-fold increase in aqueous Cd(II) removal and converted more than 53% of easily available Cd(II)-fractions (acid-extractable and reducible) to stable forms (oxidizable and residual) based on the sequential extraction results as compared to the sulfate-mediated ZVI system. Increasing SO42- concentration and ZVI dosage both demonstrated positive correlation to Cd(II) immobilization, which further reflected that hydrogenotrophic desulfuration acted an essential role in improving Cd(II) immobilization. It indicated that hydrogenotrophic desulfuration could accelerate iron corrosion and promote reactive mineral formation through biomineralization, as well as generate cadmium sulfide precipitates (CdS) to achieve excellent immobilization performance for Cd(II). Besides, this reaction was favorable under neutral pH condition. Our results highlighted the promoted effect of hydrogen-autotrophic desulfuration on ZVI corrosion to immobilize Cd(II) and offered a practicable technique in Cd(II)-polluted soil remediation.

[Simulation of carbon sequestration and timber production in Larix olgensis plantation based on CO2FIX model]. / 基于CO2FIX模型的长白落叶松人工林碳汇和木材生产模拟.

Based on datasets from plot survey and bibliographic of Larix olgensis plantations in Maoer Mountain, the CO2FIX model was used to quantitatively simulate the effects of different rotations (30, 40, 50, 60 years), site indices (12, 16, 20 m), and initial densities (2500, 3333, 4444 trees·hm-2) on the stand level carbon flows among different carbon pools (i.e., biomass carbon pool, soil carbon pool, and product carbon pool). The results showed that the CO2FIX model had high reliability for simulating the processes of L. olgensis plantation, with the average relative errors of stand biomass and volume between analog and measured values being 6.4% and 3.7%. Under the baseline conditions of initial density of 3333 trees·hm-2, site index of 16 m and rotation of 40 years, the carbon stock of total and sub-pool of L. olgensis plantation changed periodically with rotation. The total stand carbon stock and volume for L. olgensis plantation increased with the extension of rotation, the improvement of site index, and the increase of initial density. The stand carbon stock and volume would be increased by 12.2% and 31.2%, 36.7% and 67.8%, respectively, when the reference rotation was correspondingly extended by 10 and 20 years. However, if the reference rotation was shortened by 10 years, stand carbon stock and volume would be correspondingly decreased by 20.9% and 40.4%, respectively. When the initial density was set as 3333 and 4444 trees·hm-2, stand carbon stock and volume were increased by 27.8% and 50.9%, 27.4% and 49.1%, respectively. When the site index was under the range of 12 to 20 m, stand carbon stock and volume could be increased by 36.0% and 40.3%, 39.3% and 44.2%, respectively, with each increase of 4 m in site index. During one rotation, 271.57 t C per hectare could be fixed into L. olgensis plantation. At the end round of the rotation, 27.47 and 56.75 t C were transferred to soil and wood product carbon pools. Therefore, when the site condition was good, the management model with a higher initial density (4444 trees·hm-2) and longer rotation (60 years) would be more beneficial to maximizing the carbon sink and timber benefits of L. olgensis plantation.

Identification of Molecular Markers Related to Immune Infiltration in Patients with Severe Asthma: A Comprehensive Bioinformatics Analysis Based on the Human Bronchial Epithelial Transcriptome.

Background: Severe asthma (SA), a heterogeneous inflammatory disease characterized by immune cell infiltration, is particularly difficult to treat and manage. The airway epithelium is an important tissue in regulating innate and adaptive immunity, and targeting airway epithelial cell may contribute to improving the efficacy of asthma therapy. Methods: Bioinformatics methods were utilized to identify the hub genes and signaling pathways involved in SA. Experiments were performed to determine whether these hub genes and signaling pathways were affected by the differences in immune cell infiltration. Results: The weighted gene coexpression network analysis identified 14 coexpression modules, among which the blue and salmon modules exhibited the strongest associations with SA. The blue module was mainly enriched in actomyosin structure organization and was associated with regulating stem cell pluripotency signaling pathways. The salmon module was mainly involved in cornification, skin development, and glycosphingolipid biosynthesis-lacto and neolacto series. The protein-protein interaction network and module analysis identified 11 hub genes in the key modules. The CIBERSORTx algorithm revealed statistically significant differences in CD8+ T cells (P = 0.013), T follicular helper cells (P = 0.002), resting mast cells (P = 0.004), and neutrophils (P = 0.002) between patients with SA and mild-moderate asthma patients. Pearson's correlation analysis identified 11 genes that were significantly associated with a variety of immune cells. We further predicted the utility of some potential drugs and validated our results in external datasets. Conclusion: Our results may help provide a better understanding of the relationship between the airway epithelial transcriptome and clinical data of SA. And this study will help to guide the development of SA-targeted molecular therapy.

Highly sensitive RI and temperature sensor based on an asymmetric fiber coupler.

We propose and demonstrate a highly sensitive refractive index (RI) and temperature sensor based on an asymmetric fiber coupler (AFC). The AFC was fabricated by weak fusion of a pre-stretched single-mode fiber and a few-mode fiber. An ultra-sensitivity RI can be achieved near the dispersion turning point (DTP). The proposed RI sensor achieves a high RI sensitivity of -10,662.4nm/RIU within the RI range of 1.31-1.35. By packaging the AFC into polydimethylsiloxane (PDMS), the temperature sensitivity reaches 11.44 nm/°C. The proposed AFC with high RI and temperature sensitivity can be potentially used in the field of chemical monitoring, biochemical detection, and clinical diagnosis.

A missense mutation in the proprotein convertase gene furinb causes hepatic cystogenesis during liver development in zebrafish.

Hepatic cysts are fluid-filled lesions in the liver that are estimated to occur in 5% of the population. They may cause hepatomegaly and abdominal pain. Progression to secondary fibrosis, cirrhosis, or cholangiocarcinoma can lead to morbidity and mortality. Previous studies of patients and rodent models have associated hepatic cyst formation with increased proliferation and fluid secretion in cholangiocytes, which are partially due to impaired primary cilia. Congenital hepatic cysts are thought to originate from faulty bile duct development, but the underlying mechanisms are not fully understood. In a forward genetic screen, we identified a zebrafish mutant that developed hepatic cysts during larval stages. The cyst formation was not due to changes in biliary cell proliferation, bile secretion, or impairment of primary cilia. Instead, time-lapse live imaging data showed that the mutant biliary cells failed to form interconnecting bile ducts because of defects in motility and protrusive activity. Accordingly, immunostaining revealed a disorganized actin and microtubule cytoskeleton in the mutant biliary cells. By whole-genome sequencing, we determined that the cystic phenotype in the mutant was caused by a missense mutation in the furinb gene, which encodes a proprotein convertase. The mutation altered Furinb localization and caused endoplasmic reticulum (ER) stress. The cystic phenotype could be suppressed by treatment with the ER stress inhibitor 4-phenylbutyric acid and exacerbated by treatment with the ER stress inducer tunicamycin. The mutant liver also exhibited increased mammalian target of rapamycin (mTOR) signaling. Treatment with mTOR inhibitors halted cyst formation at least partially through reducing ER stress. Conclusion: Our study has established a vertebrate model for studying hepatic cystogenesis and illustrated the contribution of ER stress in the disease pathogenesis.

Modeling Kaempferol as a Potential Pharmacological Agent for COVID-19/PF Co-Occurrence Based on Bioinformatics and System Pharmacological Tools.

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology. Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities. Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways. Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.

Column study of Cd(II) removal and longevity by nitrate-mediated zero-valent iron with mixed anaerobic microorganisms.

In this study, hydrogen-autotrophic microorganisms and zero-valent iron (Fe0) were filled into columns to investigate hydrogenotrophic denitrification effect on cadmium (Cd(II)) removal and column life-span with sand, microorganisms, Fe0 and bio-Fe0 columns as controls. In terms of the experiment results, the nitrate-mediated bio-Fe0 column showed a slow Cd(II) migration rate of 0.04 cm/PV, while the values in the bio-Fe0 and Fe0 columns were 0.06 cm/PV and 0.14 cm/PV respectively, indicating much higher Cd(II) removal efficiency and longer service life of the nitrate-mediated bio-Fe0 column. The XRD and SEM-EDX results implied that this improvement was attributed to hydrogenotrophic denitrification that caused more serious iron corrosion and larger amount of secondary mineral generation (e.g., green rust, lepidocrocite and goethite). These active minerals provided more reaction sites for Cd(II) adsorption and further immobilization. In addition, the decrease of Cd(II) migration front and the increase of removal capacity along the bio-Fe0 column mediated by nitrate presented an uneven distribution in reactive zone. The latter half part was identified to be a more active region for Cd(II) immobilization. The above results indicate that the introduction of nitrate and microorganisms will improve the performance of iron-based permeable reactive barriers for the remediation of Cd(II)-containing groundwater.

Application of the Supraclavicular Artery Island Flap for Fistulas in Patients With Laryngopharyngeal Cancer With Prior Radiotherapy.

OBJECTIVE: To evaluate the effect of the supraclavicular artery island flap (SAIF) in reconstructing pharyngocutaneous fistula in patients with laryngopharyngeal cancer with prior radiotherapy. METHODS: Six patients with laryngopharyngeal cancer with pharyngocutaneous fistula due to previous radiotherapy and surgery during 2016 to 2019 were retrospectively analyzed. Initially, the fistula was treated conservatively. The SAIF was applied with double folding technique to reconstruct fistula in the patients who failed to heal after conservative treatment. RESULTS: The fistulae closed in 4 patients after conservative treatment. After SAIF operation, fistula closure was achieved in the other 2 patients who received highest dose of radiation and had largest fistulae size. The flaps grew well and there were no donor-site complications in these 2 patients. All patients achieved oral feeding without any complications. CONCLUSION: The SAIF is an effective and safe approach to reconstruct the pharyngocutaneous fistula after laryngopharyngeal surgery in patients with laryngopharyngeal cancer with previous radiotherapy, especially for those who have received high-dose radiation and have large fistula.

The Ultrasonographic Characteristics of Focal Fibrocystic Change of the Breast and Analysis of Misdiagnosis.

INTRODUCTION: To investigate ultrasonographic features and analyze causes of misdiagnosis of focal fibrocystic change (FC) of the breast. MATERIALS AND METHODS: The ultrasonographic features of 95 women (104 lesions) with postoperatively pathologically confirmed focal FC (Group 1) were retrospectively analyzed and compared with those of 105 women (107 lesions) with ductal carcinoma in situ (DCIS) (Group 2), and 164 women (177 lesions) with invasive ductal carcinoma (IDC) (Group 3). RESULTS: There were significant differences in 12 features among groups. The sizes and distributions of cystic changes among the groups were significantly different. In group 1, the incidence of cystic changes was 75%(78/104), and the main manifestation was scattered cystic changes (88.5%, 69/78) and microcapsules (81.8%, 63/78). Among focal FC lesions, 36.5% were preoperative BI-RADS classifications 4b-5 (30.8% 4b and 4c). Lesions misdiagnosed as malignant showed solid or cystic solid mixed echoes, and 70.2% of group 1 were irregularly shaped, and 63.5% had unclear edges. In group 1, 5 cases had "hyperechoic halo," 11.5% (12/104) appeared echo attenuation behind the mass, and 21 cases appeared punctate hyperechoic. CONCLUSION: FC frequently exhibits low heterogeneity, scattered microcapsules with posterior enhancement, "pit-like" or "grid-like" changes, posterior enhancement, rare hyperechoic halo, calcification, and lack of blood supply. Certain focal FC are irregularly shaped with unclear edges, with malignant signs such as crab feet and burr, hyperechoic halo, and calcification, which ultrasound BI-RADS classification may easily misdiagnose as malignant. Local magnification function should be considered, and the internal structure should be carefully observed to prevent misdiagnosis.