The clinical significance and anti-tumor role of PRKG1 in bladder cancer.

Introduction: cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear. Methods: To investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed. Results: The results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment. Conclusion: The present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

A novel laser resection approach: efficacy of rotatable bi-channel en bloc resection of bladder tumor in a pilot in-vivo study.

En bloc resection of bladder tumor (ERBT) involves removing bladder tumors and their base. Laser resection has been used to reduce complications including bleeding and obturator nerve reflex (ONR). We developed a novel approach (rotatable bi-channel en bloc resection of bladder tumor (RBC-ERBT)) and assessed its efficacy in a pilot in-vivo study to enhance laser ERBT's applicability in challenging bladder regions. In the laser RBC-ERBT procedure, lesions were excised by inserting a holmium laser through the rotating external working channel, while forceps were inserted through the internal working channel provided traction on the tissue. Fifteen laser RBC-ERBT procedures were performed in five different bladder areas of three live pigs. The technical success rate (TSR), procedure time, lesion size, occurrence of complications (bleeding, perforation, ONR), and detrusor muscle (DM) presence rate and DM thickness were evaluated. All 15 procedures were performed with a 100% TSR. The resections were successful in all bladder regions (posterior, left, right and anterior walls and dome). Median procedure time was 20 min. The resected specimen size was 10 mm × 7 mm to 17 mm × 13 mm. Mild bleeding occurred in two procedures (13.3%) but was effectively managed. No incidents of ONR or perforation were observed. Histological examination confirmed presence of DM in all specimens with a median DM thickness of 1.26 mm. Our pilot in-vivo study suggested the feasibility and effectiveness of laser RBC-ERBT for bladder tumors in various locations. This technique offers effective traction, improved visualization, and enhanced laser accessibility. Further studies are required to validate its effectiveness in humans.

Chronic oral administration of L-carnitine induces testicular injury: in vivo evidence.

PURPOSE: While L-carnitine is commonly used to treat oligoasthenozoospermia, concerns have been raised regarding its potential harm to spermatogenesis. This study aims to investigate the potential testicular toxicity of long-term oral administration of L-carnitine. METHODS: In this study, we refer to the clinical adult dosage and mode of L-carnitine administration, and after converting to mouse doses, mice were daily intragastrical administered L-carnitine to investigate whether it was harmful to the testis. The investigation involved assessing its potential testicular toxicity through histopathological staining, sperm motility analysis, and quantitative real-time PCR. RESULTS: Our results showed that L-carnitine increased sperm motility after 14 days of continuous administration, but increased luminal exfoliated spermatogenic cells occurred in the testis, and TUNEL results showed increased apoptotic cells. Compared with the control group, the mRNA expression of the spermatogenic cell marker at each stage was decreased in mice treated for 14 consecutive days of L-carnitine. After 50 days of continuous administration followed by 14 days of drug withdrawal, the total sperm motility of mice was almost 0, and a large number of abnormal eosinophilic spermatogenic cells appeared in the testis. These indicate that oral L-carnitine for more than 14 days impairs spermatogenesis in mice, and sudden discontinuation of administration results in substantial death of established spermatogenic cell populations. CONCLUSION: Our findings suggest that chronic oral administration of L-carnitine impairs spermatogenic function in the testis. The oral administration of L-carnitine to enhance sperm motility should not exceed the 2/5 point of the spermatogenic cycle.

Prevalence and genetic diversity of Anaplasma and Ehrlichia in ticks and domesticated animals in Suizhou County, Hubei Province, China.

Anaplasma and Ehrlichia are tick-borne bacterial pathogens that cause anaplasmoses and ehrlichioses in humans and animals. In this study, we examined the prevalence of Anaplasma and Ehrlichia species in ticks and domesticated animals in Suizhou County, Hubei Province in the central China. We used PCR amplification and DNA sequencing of the 16S rRNA, groEL, and gltA genes to analyze. We collected 1900 ticks, including 1981 Haemaphysalis longicornis and 9 Rhipicephalus microplus, 159 blood samples of goats (n = 152), cattle (n = 4), and dogs (n = 3) from May to August of 2023. PCR products demonstrated that Anaplasma bovis, Anaplasma capra, and an Ehrlichia species were detected in the H. longicornis with the minimum infection rates (MIR) of 1.11%, 1.32%, and 0.05%, respectively; A. bovis, A. capra, and unnamed Anaplasma sp. were detected in goats with an infection rate of 26.31%, 1.31% and 1.97%, respectively. Anaplasma and Ehrlichia species were not detected from cattle, dogs and R. microplus ticks. The genetic differences in the groEL gene sequences of the Anaplasma in the current study were large, whereas the 16S rRNA and gltA gene sequences were less disparate. This study shows that ticks and goats in Suizhou County, Hubei Province carry multiple Anaplasma species and an Ehrlichia species, with relatively higher infection rate of A. bovis in goats. Our study indicates that multiple Anaplasma and Ehrlichia species exist in ticks and goats in the central China with potential to cause human infection.

Prospective learning curve analysis of en bloc resection of bladder tumor using an ex vivo porcine model.

BACKGROUND: As a relatively new surgical technique, the learning curve of en bloc resection of bladder tumor (ERBT) in ex vivo models remains unaddressed. This study aimed to explore the learning curve of ERBT in an ex vivo porcine model. METHODS: In this prospective study, eight endoscopists without prior experience in ERBT were divided into two groups: junior endoscopists, with less than 100 transurethral resection of bladder tumor (TURBT) procedure experience, and senior endoscopists, with at least 100 TURBT procedure experience. Each endoscopist performed 30 ERBT procedures on artificial lesions in an ex vivo porcine bladder model. The procedure time, perforation, en bloc resection status, and absence of detrusor muscle (DM) were recorded. The inflection points were identified using cumulative sum (CUSUM) analysis. Procedure results were compared between the two phases and two groups. RESULTS: In all, 240 artificial lesions were successfully resected using ERBT. The CUSUM regression line indicated the inflection point at the 16th procedure for the junior endoscopists and at the 13th procedure for the senior endoscopists. In both groups, the procedure time, perforation, piecemeal resection, and DM absence rates were significantly lower in the consolidation phase than in the initial phase. The procedure time for the senior endoscopists was lower than for the junior endoscopists in both phases. CONCLUSIONS: ERBT performance improved significantly after reaching the inflection point of the learning curve in the ex vivo model. We recommend a minimum of 16 ERBT procedures in ex vivo models for urologists with less than 100 TURBT experience and a minimum of 13 procedures for those with at least 100 TURBT experience before advancing to live animal training or supervised clinical practice.

Embryo Transfer Strategies for Women with Recurrent Implantation Failure During the Frozen-thawed Embryo Transfer Cycles: Sequential Embryo Transfer or Double-blastocyst Transfer?

OBJECTIVE: Both sequential embryo transfer (SeET) and double-blastocyst transfer (DBT) can serve as embryo transfer strategies for women with recurrent implantation failure (RIF). This study aims to compare the effects of SeET and DBT on pregnancy outcomes. METHODS: Totally, 261 frozen-thawed embryo transfer cycles of 243 RIF women were included in this multicenter retrospective analysis. According to different embryo quality and transfer strategies, they were divided into four groups: group A, good-quality SeET (GQ-SeET, n=38 cycles); group B, poor-quality or mixed-quality SeET (PQ/MQ-SeET, n=31 cycles); group C, good-quality DBT (GQ-DBT, n=121 cycles); and group D, poor-quality or mixed-quality DBT (PQ/MQ-DBT, n=71 cycles). The main outcome, clinical pregnancy rate, was compared, and the generalized estimating equation (GEE) model was used to correct potential confounders that might impact pregnancy outcomes. RESULTS: GQ-DBT achieved a significantly higher clinical pregnancy rate (aOR 2.588, 95% CI 1.267-5.284, P=0.009) and live birth rate (aOR 3.082, 95% CI 1.482-6.412, P=0.003) than PQ/MQ-DBT. Similarly, the clinical pregnancy rate was significantly higher in GQ-SeET than in PQ/MQ-SeET (aOR 4.047, 95% CI 1.218-13.450, P=0.023). The pregnancy outcomes of GQ-SeET were not significantly different from those of GQ-DBT, and the same results were found between PQ/MQ-SeET and PQ/MQ-DBT. CONCLUSION: SeET relative to DBT did not seem to improve pregnancy outcomes for RIF patients if the embryo quality was comparable between the two groups. Better clinical pregnancy outcomes could be obtained by transferring good-quality embryos, no matter whether in SeET or DBT. Embryo quality plays a more important role in pregnancy outcomes for RIF patients.

Contributing Risk Factors to Self-Contamination During the Process of Donning and Doffing Personal Protective Equipment.

OBJECTIVE: The goal of this study is to explore the risk factors associated with self-contamination points during personal protective equipment (PPE) donning and doffing among health care workers (HCWs). METHODS: In total, 116 HCWs were randomly sampled and trained to don and doff the whole PPE set. We smeared the whole PPE set with the fluorescent powder. After each participant finished PPE doffing, the whole body was irradiated with ultraviolet light in order to detect contamination points and record the position and quantity. Sociodemographic characteristics and previous infection prevention control (IPC) training experience, among others, were collected by using electronic questionnaires. Poisson regression was used in identifying risk factors that are associated with the number of contamination points, and the relative risk (RR) and its 95% confidence interval (CI) were calculated. RESULTS: About 78.5% of participants were contaminated. Ever training experience (RR = 0.37; 0.26, 0.52), clinical departments (RR = 0.67; 0.49, 0.93), body mass index (BMI) (RR = 1.09; 1.01, 1.18), and shoulder width (RR = 1.07; 1.01, 1.13) were associated with the number of contamination points. CONCLUSIONS: Previous IPC training experience, department types, BMI, and shoulder width were associated with self-contamination points after the PPE was removed.

Anti-galvanic reaction induced interfacial engineering to reconstruct ternary colloid satellite platform for exceptionally high-performance redox-responsive sensor.

The anti-galvanic reaction (AGR), which is a classic galvanic reaction (GR) with an opposite effect, is a unique phenomenon associated with the quantum size effect. This reaction involves the interaction between metal ions and nanoclusters, offering opportunities to create well-defined nanomaterials and diverse reductive behavior. In hence, in our work, we utilize the AGR to generate gold (Au), silver (Ag), and copper (Cu) satellite nanoclusters which have superior electromagnetic properties for Surface-enhanced Raman spectroscopy (SERS) sensor. As the AGR process, weak oxidant Cu2+ is selected to etched matrix Au@Ag NPs, reduced to Cu(0) or Cu(1) and generated the ultrasmall metal nanoparticles (Ag). To facilitate the AGR, we introduce the nucleophilic thiol 4-mercaptopyridine (4-Mpy) to bridge the metal ions or ultrasmall metal nanoparticles to reconstruct the satellite nanoclusters. These experimental displays that the AGR based biosensors has highly sensitivity for reductive molecule glucose. The liner ranges from 1 mmol/L to 1 nmol/L and alongs with a correlation coefficient and detection limit (LOD) of 0.999 and 0.14 nmol/L. Moreover, the AGR based biosensors exhibits remarkable stability and high repeatability with RSD 1.3 %. The food samples are tested to further investigate the accuracy and reliability of the method, which provides a novel and effective SERS method for the reduction molecules detection.

Comprehensive Analysis of Prognostic Value and Immune Infiltration of TFAP2 Family Members in Bladder Cancer from Database and FFPE Sample.

Background: Bladder cancer (BLCA) is one of the common malignant tumors worldwide. Recent studies have shown that Transcription factor activating protein-2(TFAP2) family proteins plays a bidirectional regulatory role in the process of tumorigenesis versus evolution by regulating the expression of tumor associated genes. However, little is known about the function of distinct TFAP2s proteins in patient with BLCA. Methods: Formalin-fixed paraffin-embedded (FFPE) sample tissues and clinical data of 240 patients with bladder cancer were collected for immunohistochemical analysis. The Human Protein Atlas, Gene Expression Profiling Interactive Analysis (GEPIA), Shiny Methylation Analysis Resource Tool (SMART), Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, TIMER and CIBERSORT were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of TFAP2 family in patients with BLCA. Results: Our study found that TFAP2 family proteins are generally expressed higher in BLCA tissues than in normal tissues. However, they show different trends in the growth, metastasis and survival prognosis of BLCA. TFAP2A and TFAP2C was associated with worse clinical stage and prognosis in BLCA patients, while TFAP2B, TFAP2D and TFAP2E showed the opposite trend. Importantly, the functions of the differentially expressed TFAP2s were primarily related to the developmental process, reproductive process, response to stimulus and immune system process, etc. Moreover, TFAP2 family was significantly correlated with the infiltration of six immune cell types and might regulate TAM polarization. Conclusion: TFAP2 family might be an important regulator of immune cell infiltration and a valuable prognostic biomarker in patients with BLCA.

Rotatable Bi-Channel En Bloc Resection of Bladder Tumor for Non-Muscle-Invasive Bladder Cancer in an Ex Vivo Porcine Model.

En bloc resection of bladder tumor (ERBT) is a promising alternative for non-muscle-invasive bladder cancer management. However, the tumor characteristics and surgeon's experience influence its application. Therefore, in this pilot study, we developed a technique called "rotatable bi-channel en bloc resection of bladder tumor (RBC-ERBT)" and assessed its feasibility, efficacy, and safety compared with those of conventional ERBT. In an ex vivo porcine bladder model, 160 bladder lesions of varying morphologies (exophytic and flat) and sizes (1 and 2 cm) were created and evenly distributed across different locations. A total of 160 procedures were performed, with the ERBT and RBC-ERBT group each exhibiting 80 lesions. RBC-ERBT had a significantly higher technical success rate than ERBT (98.8% vs. 77.5%) for exophytic and flat lesions of both sizes and dome lesions. The procedure time was significantly shorter in the RBC-ERBT group, particularly for flat lesions, lesions with a 2 cm diameter, and lesions located at the dome. RBC-ERBT had a significantly lower piecemeal resection rate than ERBT (0% vs. 18.8%). The incidence of perforation or detrusor muscle sampling did not differ between the groups. Compared with conventional ERBT, RBC-ERBT offered improved success rates, reduced resection times, and effective management of challenging lesions.

The Efficacy and Safety of Teprotumumab in Thyroid Eye Disease: Evidence from Randomized Controlled Trials.

In this study, we conducted a meta-analysis to assess the efficacy and safety of teprotumumab in treating thyroid eye disease. We searched the Cochrane Library, PubMed, and Embase databases from inception to May 25, 2022, and included all randomized controlled trials. Odds ratios (ORs) were calculated using fixed- or random-effect models. A total of three studies involving 341 patients were identified. Overall, the analysis revealed that teprotumumab demonstrated superior integrated proptosis response compared to placebo in both the intention-to-treat (ITT) population (OR = 17.81, 95% CI = [10.32, 30.76], I2 = 50%) and per-protocol population (OR = 24.53, 95% CI = [12.96, 46.45], I2 = 14%). Furthermore, patients receiving teprotumumab showed significant improvement in overall response (OR = 8.35, 95% CI = [4.74, 14.71], I2 = 79%), diplopia response (OR = 5.53, 95% CI = [3.24, 9.44], I2 = 0%), and achieving a clinical activity score (CAS) of 0 or 1 (OR = 6.26, 95% CI = [3.87, 10.12], I2 = 0%). Moreover, patients treated with teprotumumab experienced greater improvements in proptosis (MD = -2.49, 95% CI = [-2.54, -2.45], I2 = 98%) and Graves' ophthalmopathy-specific quality of life (GO-QOL, MD = 11.48, 95% CI = [11.03, 11.93], I2 = 95%). However, it is important to note that patients receiving teprotumumab had a higher risk of adverse events, including serious adverse events, gastrointestinal adverse reactions, and muscle spasms. In summary, teprotumumab demonstrated greater improvement in proptosis response, proptosis, diplopia response, overall response, GO-QOL, and CAS. Nonetheless, it should be considered that its use is associated with a higher risk of adverse events.

Vacuum sealing drainage to treat Fournier's gangrene.

BACKGROUND: Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier's gangrene (FG). METHODS: Data of patients surgically treated for FG were retrospectively analyzed. RESULTS: Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28-74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. CONCLUSION: VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.

Design of competition nanoreactor with shell-isolated colloidal plasmonic nanomaterials for quantitative sensor platform.

Shell-isolated colloid plasmonic nanomaterials-based nanoreactor is a well-established platform widely applied in catalyst or Surface Enhanced Raman Scattering (SERS) sensors. The potentials versatility of nanoreactor platform is mainly implemented by the well-defined and tailorable structure of colloid plasmonic nanomaterials. Currently, a competitive conjugative-mediated nanoreactor is introduced to determine glucose with SERS. Glucose-conjugating nanoreactor, as convertors of the sensors, are constructed by coordinated deposition colloidal gold nanoparticles with sodium nitroprusside framework (Au@SNF) and covalently bonded 4-mercaptopyridine (4-Mpy) with self-assembly strategy. The nanoreactor contained the signal-amplifier Au@SNF NPs, conjugative-mediated signal receiver 4-Mpy, and signal internal standard molecular CN-. In addition to well-defined morphology and functionality, conjugative-mediated and internal standards method are also employed to benefit the nanoreactor. The two-parameter strategy significantly improves the signal indication and correction. Using this proposed platform, the competitive-mediated nanoreactor provides a quantitative SERS detection of glucose, and extends the applicability of SERS in more complicated and reproducibility analysis. Meanwhile, the nanoreactor based sensors also exhibited better properties to detect glucose in various food samples and bio-samples which provided strongly appliance for glucose sensors.

Evolution and Reassortment of H6 Subtype Avian Influenza Viruses.

The H6 subtype of avian influenza virus (H6 AIV) is the most detected AIV subtype in poultry and wild birds. It causes economic losses to the poultry industry, and the most important, H6 AIV may have the ability to infect mammals, which is a great threat to public health security. In addition, the H6 subtype can serve as a precursor to providing internal genes for other highly pathogenic AIVs, posing a potential threat. H6 AIV currently face to the high positive detection rate and harmless nature of H6 AIV and because not highly effective H6 subtype vaccine available on the market. In this study, we focused on the prevalence of H6 AIV in poultry and wild birds, phylogenetic analysis, genetic variation characteristics, selection analysis, and prevention and control to provide relevant references for the scientific prevention and control of H6 AIV in future.

Dermoscopy in Mycobacterium marinum infection and its correlation with clinical and histopathological features: a prospective observational study.

BACKGROUND: Mycobacterium marinum is a nontuberculous mycobacterium and a conditional pathogen to humans, which can be inoculated directly and cause chronic skin granulomas. Dermoscopy has been applied to other granulomatous skin diseases, but not to M. marinum infection. AIM: To explore the dermoscopic features of M. marinum infection, and its correlation with clinical and histopathological features. METHODS: In total, 27 lesions from 27 patients (19 women, 8 men, age range 28-71 years) diagnosed with M. marinum infection were identified by clinical examination, histopathological results, PCR sequencing and mycobacterial culture in the dermatology outpatient department of our hospital from March 2020 to February 2022. The dermoscopy images and pathological characteristics were analysed. RESULTS: Lesions were located on the hands, forearms and upper arms. The following dermoscopic features were observed: yellowish-orange structureless areas (85·2%), white striped structures (59·3%), follicular plugs (29·6%), yellowish oval clods (14·8%) and reddish or pinkish areas (14·8%). Vessel structures were visible in all cases: long hairpin vessels (81·5%), corkscrew vessels (25·9%), comma-shaped vessels (22·2%) and linear vessels (22·2%). CONCLUSION: Yellowish-orange structureless areas, white striped structures and long hairpin vessels are the most common dermoscopic features of M. marinum infection. Thus, dermoscopy could be used as a noninvasive auxiliary diagnostic method to provide a diagnostic basis for this disease.

Creatine chemical exchange saturation transfer (CEST) CMR imaging reveals myocardial early involvement in idiopathic inflammatory myopathy at 3T: feasibility and initial experience.

OBJECTIVES: To measure creatine distribution in idiopathic inflammatory myopathy (IIM) patients' myocardial segments and investigate whether cardiovascular magnetic resonance (CMR) chemical exchange saturation transfer (CEST) creatine mapping can detect subclinical myocardial changes, CEST's ability was further compared with other conventional CMR mapping sequences. METHODS: Forty IIM patients (53.5 ± 10.5 years, 26 males) and eight healthy controls (35.4 ± 6 years, 5 males) underwent CMR scans on a 3.0-T MR scanner. Patients with IIM were further classified into two subgroups according to cardiac troponin T (cTn-T) values: the elevated cTn-T subgroup (n = 14) and the normal cTn-T subgroup (n = 26). Cine imaging, T2 SPAIR, LGE imaging, T1 mapping, T2 mapping, and Cr (creatine) CEST were performed. RESULTS: Cr mapping showed significantly reduced creatine in IIM patients among global myocardium (IIM: 0.109 ± 0.063, controls: 0.121 ± 0.021, p < 0.05), and decreased creatine signals were detected in all 16 cardiac segments (p < 0.05). Patients also had significantly prolonged native T1 and decreased enhanced T1 values in each cardiac segment (p < 0.05). There was no significant difference of LVEF and T2 values between IIM patients and controls. Between the two subgroups, elevated cTn-T was linked with creatine and extracellular volume fraction (ECV) values, providing a global average creatine signal of 0.107 vs 0.112 (p < 0.05) and 24.7 vs 32.4 (p < 0.05). CONCLUSION: Creatine CEST mapping can detect early-stage heart involvement with negative LGE findings in IIM. Compared with T1 mapping, CEST provides increased sensitivity to ECV measurement, making it significantly better than T1, and a promising CMR sequence for screening subclinical myocardial damage. KEY POINTS: • IIM patients with potential or ongoing heart involvement, elevated ECV, and reduced Cr CEST values could provide valuable information. • ECV and Cr CEST values were closely related to elevated cTn-T.

Zika virus infection triggers lipophagy by stimulating the AMPK-ULK1 signaling in human hepatoma cells.

Zika virus (ZIKV) is a globally transmitted mosquito-borne pathogen, and no effective treatment or vaccine is available yet. Lipophagy, a selective autophagy targeting lipid droplets (LDs), is an emerging subject in cellular lipid metabolism and energy homeostasis. However, the regulatory mechanism of lipid metabolism and the role of lipophagy in Zika virus infection remain largely unknown. Here, we demonstrated that ZIKV induced lipophagy by activating unc-51-like kinase 1 (ULK1) through activation of 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) in Huh7 cells. Upon ZIKV infection, the average size and triglyceride content of LDs significantly decreased. Moreover, ZIKV infection significantly increased lysosomal biosynthesis and LD-lysosome fusion. The activities of AMPK at Thr-172 and ULK1 at Ser-556 were increased in ZIKV-infected cells and closely correlated with lipophagy induction. Silencing of AMPK expression inhibited ZIKV infection, autophagy induction, and LD-lysosome fusion and decreased the triglyceride content of the cells. The activities of mammalian target of rapamycin (mTOR) at Ser-2448 and ULK1 at Ser-757 were suppressed independently of AMPK during ZIKV infection. Therefore, ZIKV infection triggers AMPK-mediated lipophagy, and the LD-related lipid metabolism during ZIKV infection is mainly regulated via the AMPK-ULK1 signaling pathway.

Lipid Droplets and Their Participation in Zika Virus Infection.

Lipid droplets (LDs) are highly conserved and dynamic intracellular organelles. Their functions are not limited to serving as neutral lipid reservoirs; they also participate in non-energy storage functions, such as cell lipid metabolism, protection from cell stresses, maintaining protein homeostasis, and regulating nuclear function. During a Zika virus (ZIKV) infection, the viruses hijack the LDs to provide energy and lipid sources for viral replication. The co-localization of ZIKV capsid (C) protein with LDs supports its role as a virus replication platform and a key compartment for promoting the generation of progeny virus particles. However, in view of the multiple functions of LDs, their role in ZIKV infection needs further elucidation. Here, we review the basic mechanism of LD biogenesis and biological functions and discuss how ZIKV infection utilizes these effects of LDs to facilitate virus replication, along with the future application strategy of developing new antiviral drugs based on the interaction of ZIKV with LDs.

Highly crosslinking core-shell magnetic nanocomposites based catalyst and heat free polymerization for isolation of glycoprotein.

New approaches for the engineering of well-defined, pore modality, and multi-chemical functionality nanocomposites are crucial to generate the next generation of functional materials with recoverable and easy preparation properties. Here, a catalyst and heat free polymerization reaction is exploited and fabricated zwitterionic system around magnetic nanoparticles. N-aminoethyl piperazine propane sulfonate (AEPPS) and dopamine (DA) are introduced as the zwitterionic system, which provided abundant zwitterionic groups (NH2, SO3-, N+) and strong adhesion and various oxidation state properties. And that, the zwitterionic engineering will assemble between AEPPS and DA whereby Schiff base formation or Michael type addition. Whereafter, a series of sophisticated array of microscopic, spectroscopic, and structure techniques verify the formation of highly crosslinking internal zwitterionic architectures, well-defined core-shell structure, and better porosity. The zwitterionic structure-function relationships and striking porous structure are explored in a multi-interaction adsorption assay. The adsorption capacity of the magnetic nanocomposites was 1065.8 mg/g. And that, the system exhibited with hydrophilic-hydrophobic activity towards glycoprotein and better performance to bioactive protein (Ig-G) isolation form human whole blood sample. The synergistic enhancement interaction in hydrophilic target enrichment, easy preparation, and soft substrate properties of the AEPPS-DA zwitterionic materials make them intriguing candidates for sustainable biomedical loading and chromatographic separation.

Gender Differential Expression of AR/miR-21 Signaling Axis and Its Protective Effect on Renal Ischemia-Reperfusion Injury.

Objective: The aim of this study was to investigate gender differences after renal ischemia-reperfusion injury in mice and the effects of androgen receptor (AR) and microRNA-21 (miR-21) on apoptosis in renal ischemia-reperfusion injury. Methods: Renal ischemia-reperfusion injury model was induced by 45 min of bilateral renal artery ischemia and reperfusion. BALB/c mice were randomly divided into groups according to different experimental protocols. The levels of renal function were evaluated by serum creatinine and blood urea nitrogen. TUNEL staining was used to analyze the pathological changes and apoptosis levels of renal tissue, and western blotting and qPCR were used to detect the expressions of miR-21, AR, PDCD4 and caspase3. Results: After renal ischemia-reperfusion injury in mice with different genders, the levels of plasma urea nitrogen and creatinine in female and male mice increased, the histopathological score increased, and TUNEL staining in renal tissue indicated increased apoptosis. The expressions of miR-21, PDCD4, and active caspase-3 protein were up-regulated. The above trend was more pronounced in male mice, and a significant decrease in AR mRNA expression was detected. Silencing the expression of AR aggravated the decline of renal function and renal tubular injury after renal ischemia in mice. The expression of PDCD4 and active caspase-3 increased, while the level of miR-21 was correspondingly decreased. Up-regulation of miR-21 expression by pre-miR-21 could negatively regulate PDCD4, reduce the expression level of active caspase3, and yet induce AR expression accordingly. MiR-21 alleviated renal ischemia-reperfusion injury by inhibiting renal tubular epithelial cell apoptosis. The effect of antagomiR-21 was the opposite, which aggravated renal ischemia-reperfusion injury. Conclusion: There are gender differences in renal ischemia-reperfusion injury. Male mice are more susceptible to renal ischemia-reperfusion injury than female. Silencing AR expression or down-regulating the level of miR-21 can promote the expression of PDCD4 and apoptosis protein caspase3, thereby aggravating ischemia-reperfusion injury in mice. The protective effect of AR and miR-21 in renal ischemia-reperfusion injury has a certain synergy.