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Abstract Gremlin 1 (GREM1) can regulate the development of many cancers. However, a few studies have revealed the role of GREM1 in bladder cancer (BC). To evaluate the expression and potential function of GREM1 in bladder cancer, we used R version 3.6.3 and related packages to analyze the data from common databases. Samples from our institution were assessed by immunohistochemical staining (IHC), which was approved by the Institutional Ethics Committee (K20220830). GREM1 was highly expressed in BC tissues according to the TCGA and IHC data. Data from TCGA, GSE31684, GSE32894, and IHC showed that GREM1 has significant prognostic value for BC patients. GREM1 is involved in immune and metabolism-related pathways. According to the TIDE algorithm, 61.0% of patients with low GREM1 expression responded well to immunotherapy, compared to only 13.3% in the high GREM1 expression group. High GREM1 expression was associated with sensitivity to cisplatin, docetaxel, gemcitabine, and vinblastine. Thus, GREM1 can predict prognosis and responses to immunotherapy and chemotherapy in BC patients, making it a potential biomarker and therapeutic target.

ABSTRACT The rapid expansion of antibiotic-resistant bacterial diseases is a global burden on public health. It makes sense to repurpose and reposition already-approved medications for use as supplementary agents in synergistic combinations with existing antibiotics. Here, we demonstrate that the anthelmintic drug nitazoxanide (NTZ) synergistically enhances the effectiveness of the lipopeptide antibiotic polymyxin B in inhibiting gram-negative bacteria, including those resistant to polymyxin B. Mechanistic investigations revealed that nitazoxanide inhibited calcium influx and cell membrane depolarization, enhanced the affinity between polymyxin B and the extracellular membrane, and promoted intracellular ATP depletion and an increase in reactive oxygen species (ROS), thus enhancing the penetration and disruption of the Escherichia coli cell membrane by polymyxin B. The transcriptomic analysis revealed that the combination resulted in energy depletion by inhibiting both aerobic and anaerobic respiration patterns in bacterial cells. The increased bactericidal effect of polymyxin B on the E. coli ∆nuoC strain further indicates that NuoC could be a promising target for nitazoxanide. Furthermore, the combination of nitazoxanide and polymyxin B showed promising therapeutic effects in a mouse infection model infected with E. coli. Taken together, these results demonstrate the potential of nitazoxanide as a novel adjuvant to polymyxin B, to overcome antibiotic resistance and improve therapeutic outcomes in refractory infections.IMPORTANCEThe rapid spread of antibiotic-resistant bacteria poses a serious threat to public health. The search for potential compounds that can increase the antibacterial activity of existing antibiotics is a promising strategy for addressing this issue. Here, the synergistic activity of the FDA-approved agent nitazoxanide (NTZ) combined with polymyxin B was investigated in vitro using checkerboard assays and time-kill curves. The synergistic mechanisms of the combination of nitazoxanide and polymyxin B were explored by fluorescent dye, transmission electron microscopy (TEM), and transcriptomic analysis. The synergistic efficacy was evaluated in vivo by the Escherichia coli and mouse sepsis models. These results suggested that nitazoxanide, as a promising antibiotic adjuvant, can effectively enhance polymyxin B activity, providing a potential strategy for treating multidrug-resistant bacteria.

In this study, carbon-quantum-dot (CQD)-decorated TiO2 was prepared using an ultrasonic doping method and applied in the photocatalytic degradation of naphthalene under sunlight irradiation. The CQDs were synthesized from a typical macroalgae via diluted sulfuric acid pretreatment and hydrothermal synthesis using an optimal design, i.e., 3 wt% and 200 °C, respectively. The CQD/TiO2 composite remarkably enhanced the photocatalytic activity. The degradation of naphthalene under a visible light environment indicated that there is a synergistic mechanism between the CQDs and TiO2, in which the generation of reactive oxygen species is significantly triggered; in addition, the N that originated from the macroalgae accelerated the photocatalytic efficiency. Kinetic analysis showed that the photocatalytic behavior of the CQD/TiO2 composite followed a pseudo-first-order equation. Consequently, our combined experimental approach not only provides a facile pretreatment process for bio-CQDs synthesis, but also delivers a suitable TiO2 photocatalyst for the visible environment along with critical insights into the development of harmful macroalgae resources.

Abstract The stacking of twisted two-dimensional (2D) layered materials has led to the creation of moiré superlattices, which have become a new platform for the study of quantum optics. The strong coupling of moiré superlattices can result in flat minibands that boost electronic interactions and generate interesting strongly correlated states, including unconventional superconductivity, Mott insulating states, and moiré excitons. However, the impact of adjusting and localizing moiré excitons in Van der Waals heterostructures has yet to be explored experimentally. Here, we present experimental evidence of the localization-enhanced moiré excitons in the twisted WSe2/WS2/WSe2 heterotrilayer with type-II band alignments. At low temperatures, we observed multiple excitons splitting in the twisted WSe2/WS2/WSe2 heterotrilayer, which is manifested as multiple sharp emission lines, in stark contrast to the moiré excitonic behavior of the twisted WSe2/WS2 heterobilayer (which has a linewidth 4 times wider). This is due to the enhancement of the two moiré potentials in the twisted heterotrilayer, enabling highly localized moiré excitons at the interface. The confinement effect of moiré potential on moiré excitons is further demonstrated by changes in temperature, laser power, and valley polarization. Our findings offer a new approach for localizing moiré excitons in twist-angle heterostructures, which has the potential for the development of coherent quantum light emitters.

The moiré intralayer excitons in the twisted WSe2/WSe2 homobilayers superlattices were successfully observed and confirmed the existence of moiré intralayer excitons.

African swine fever (ASF) is a contagious infectious disease with high lethality which continuously threatens the global pig industry causing huge economic losses. Currently, there are no commercially available vaccines or antiviral drugs that can effectively control ASF. The pathogen of ASF, ASF virus (ASFV) is a double-stranded DNA virus with a genome ranging from 170 to 193 kb and 151 to 167 open reading frames in various strains, which encodes 150–200 proteins. An effective method of monitoring ASFV antibodies, and specific antibodies against ASFV to promote the development of prevention techniques are urgently needed. In the present study, pK205R of ASFV was successfully expressed in mammalian cells using a suspension culture system. An indirect enzyme-linked immunosorbent assay (ELISA) based on the purified pK205R was established and optimized. The monoclonal antibody (mAb) against pK205R recognized a conservative linear epitope (2VEPREQFFQDLLSAV16) and exhibited specific reactivity, which was conducive to the identification of the recombinant porcine reproductive and respiratory syndrome virus (PRRSV) expressing pK205R. The ELISA method efficiently detected clinical ASFV infection and revealed good application prospects in monitoring the antibody level in vivo for recombinant PRRSV live vector virus expressing the ASFV antigen protein. The determination of the conserved linear epitope of pK205R would contribute to further research on the structural biology and function of pK205R. The indirect ELISA method and mAb against ASFV pK205R revealed efficient detection and promising application prospects, making them ideal for epidemiological surveillance and vaccine research on ASF.

Cuproptosis is a fresh form of the copper-elesclomol-triggered, mitochondrial tricarboxylic acid (TCA) dependent cell death. Yet, the subsumed mechanism of cuproptosis-associated lncRNAs in carcinoma is not wholly clarified. Here, We appraised 580 cuproptosis-associated lncRNAs in sarcoma and thereafter construed a module composing of 6 cuproptosis lncRNAs, entitled CuLncScore, utilizing a machine learning methodology. It could outstandingly discern the prognosis of patients in parallel with discriminating tumor immune microenvironment traits. Moreover, we simulate the classification system of cuproptosis lncRNAs by unsupervised learning method to facilitate differentiation of clinical denouement and immunotherapy modality options. Notably, Our Taizhou cohort validated the stability of CuLncScore and the classification system. Taking a step further, we checked these 6 cuproptosis lncRNAs by Quantitative real-time polymerase chain reaction (qRT-PCR) to ascertain their authenticity. All told, our investigations highlight that cuproptosis lncRNAs are involved in various components of sarcoma and assist in the formation of the tumor immune microenvironment. These results provide partial insights to further comprehend the molecular mechanisms of cuproptosis lncRNAs in sarcoma and could be helpful for the development of personalized therapeutic strategies targeting cuproptosis or cuproptosis lncRNAs.

The fate of a drug is not only the process of drug metabolism in vivo and in vitro but also the homeostasis of drug-exposed microbial communities may be disturbed. Anticoccidial drugs are widely used to combat the detrimental effects of protozoan parasites in the poultry industry. Salinomycin and ethanamizuril belong to two different classes of anticoccidial drugs. The effect of salinomycin and ethanamizuril on the microbiota of cecal content, manure compost, and soil remains unknown. Our results showed that although both salinomycin and ethanamizuril treatments suppressed some opportunistic pathogens, they failed to repair the great changes in chicken cecal microbial compositions caused by coccidia infection. Subsequently, the metabolite5 profiling of cecal content by LC-MS/MS analyses confirmed the great impact of coccidia infection on chicken cecum and showed that histidine metabolism may be the main action pathway of salinomycin, and aminoacyl tRNA biosynthesis may be the major regulatory mechanism of ethanamizuril. The microbial community of manure compost showed a mild response to ethanamizuril treatment, but ethanamizuril in soil could promote Actinobacteria reproduction, which may inhibit other taxonomic bacteria. When the soil and manure were exposed to salinomycin, the Proteobacteria abundance of microbial communities showed a significant increase, which suggested that salinomycin may improve the ability of the microbiota to utilize carbon sources. This hypothesis was confirmed by a BIOLOG ECO microplate analysis. In the animal model of coccidia infection, the treatment of salinomycin and ethanamizuril may reconstruct a new equilibrium of the intestinal microbiota. In an in vitro environment, the effect of ethanamizuril on composting and soil microbiota seems to be slight. However, salinomycin has a great impact on the microbial communities of manure composting and soil. In particular, the promoting effect of salinomycin on Proteobacteria phylum should be further concerned. In general, salinomycin and ethanamizuril have diverse effects on various microbial communities.

Achieving efficient photoelectrochemical cells requires insights into the ion kinetics at the surface of photoelectrode. Here, the authors show a new platform for investigating strong coupling between hydroxide ions and surface charge carriers by using monolayer InSe as the anode with high photocurrent density.

Abstract Background Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. This study was designed to evaluate the subchronic toxicity of ethanamizuril in beagle dogs at doses of 12, 60 or 300 mg/kg/day in diet for 90 days. Results Ethanamizuril was well tolerated at low and middle dosages in beagle dogs, and no drug-related toxical effects were observaed in terms of survival, clinical observations, organs weight and damage in these dose groups. However, in high dose administration group, food consumption and histologic changes in kidneys were noticed in both sexes of beagle dog, although the renal lesions were finally resolved at the end of 4 weeks exposure of ethanamizuril. Conclusions No-observed-adverse-effect level (NOAEL) was considered for ethanamizuril at dose of 60 mg/kg/day in Beagle dog. This result added toxicity effects of ethanamizuril to the safety database, which might guide safely using of ethanamizuril as a novel coccidiostat.

Abstract Background Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has been become an important procedure for the diagnosis and staging of lung cancer. Our research identified the effects of different pathological preparation on the diagnosis of lung cancer for specimens obtained by biopsy. Methods Patients were clinically considered if lung cancer was accompanied by mediastinal or hilar lymph node enlargement between March 2014 and November 2017. Specimens obtained by EBUS-TBNA were treated by three methods: traditional smear cytology, liquid-based cytology (LBC) and histopathology. Results Of a total of 154 puncture sites from 153 patients, the total positive rate of combination for the three pathological treatment types (histopathology, direct traditional smear, and LBC) was 77.3%. The diagnostic positive rate for histopathology was 68.6%, direct traditional smear was 65.6%, and LBC was 60.4%; there was no significant differences among the three single pathological treatment types (P = 0.29), but there was a statistically significant difference between the combination of three treatments and any single pathological treatment type (P = 0.01). The diagnostic sensitivities of histopathology combined with traditional smear and histopathology combined LBC were 94.4 and 92.8%, respectively, the specificities and PPVs were both 100%, and the diagnostic accuracies were 95.5 and 94.2%, respectively; the sensitivities, specificities and diagnostic accuracies above were all higher than those of single specimen treatment and lower than those of the three combined. Conclusion When EBUS-TBNA is used for the diagnosis and staging of lung cancer, the use of histopathological sections combined with direct cytological smear should be sufficient and is the most economical choice.

Purpose. To elucidate the clinical and prognostic role of PDZ and LIM domain protein (PDLIM) genes and the association to epithelial-mesenchymal transition (EMT) and immune cell infiltration in patients with prostate cancer (PRAD). Methods. The data of RNA-seq, DNA methylation, and clinical features of PRAD patients were collected from The Cancer Genome Atlas (TCGA) database to define the prognostic value of PDLIM gene expression and the association with EMT and immune cell infiltration. A tissue microarray including 134 radical prostatectomy specimens was served as validation by immunohistochemistry (IHC) staining analysis. Results. The mRNA levels of PDLIM1/2/3/4/6/7 were significantly downregulated, while PDLIM5 was upregulated in PRAD (P

Since 2018, the outbreak and prevalence of the African swine fever virus (ASFV) in China have caused huge economic losses. Less virulent ASFVs emerged in 2020, which led to difficulties and challenges for early diagnosis and control of African swine fever (ASF) in China. An effective method of monitoring ASFV antibodies and specific antibodies against ASFV to promote the development of prevention techniques are urgently needed. In the present study, ASFV p17 was successfully expressed in CHO cells using a suspension culture system. An indirect enzyme-linked immunosorbent assay (ELISA) based on purified p17 was established and optimized. The monoclonal antibody (mAb) against p17 recognized a conservative linear epitope (3TETSPLLSH11) and exhibited specific reactivity, which was conducive to the identification of recombinant porcine reproductive and respiratory syndrome virus (PRRSV) expressing p17. The ELISA method efficiently detected clinical ASFV infection and effectively monitored the antibody levels in vivo after recombinant PRRSV live vector virus expressing p17 vaccination. Overall, the determination of the conserved linear epitope of p17 would contribute to the in-depth exploration of the biological function of the ASFV antigen protein. The indirect ELISA method and mAb against ASFV p17 revealed efficient detection and promising application prospects, making them ideal for epidemiological surveillance and vaccine research on ASF.

ASF has caused huge economic losses to China’s swine industry. As clinical symptoms of ASF were difficult to distinguish from classical swine fever and porcine reproductive and respiratory syndrome (PRRS), rapid and effective differential diagnosis of ASFV seems very important to control the spread of the disease. In this study, the ASFV E248R gene was selected to be the target for establishing a real-time PCR method. TaqMan real-time PCR for the detection of ASFV E248R gene did not cross-react with other porcine viruses that could cause similar symptoms. The results of the repeatability test showed that the coefficients of variation between and within groups were lower than 1.977%. This method can be used for the rapid detection and early diagnosis of ASF. Meanwhile, the recombinant PRRS virus (PRRSV)-expressing E248R gene of ASFV was constructed and rescued by using the reverse genetic platform of live-attenuated PRRSV vaccine. The ASFV E248R gene can be detected by using this real-time PCR detection method, confirming that the ASFV E248R gene could be stably amplified in PRRSV genome at least 20 cell passages. The detection methods can be used for the efficient detection of the ASFV infection and recombinant PRRSV live vector virus-expressing ASFV antigen protein.

To reduce the efforts of human in browsing long surveillance videos, synopsis videos are proposed. Traditional synopsis video generation methods condense most of the activities in the video by simultaneously showing several actions, even when they originally occurred at different times. This inevitably causes ignorance of temporal relationship among objects. For example, two persons walk shoulder to shoulder and they are detected and tracked separately, but in the synopsis they never ‘met’. In this study, a trajectory mapping model is defined, whose energy function includes not only the cost caused by the synopsis video, but that of the original video. In this way, it tries to make the relationship between objects of the original video consistent with that of the synopsis. Finally, the video synopsis is generated by an energy minimisation method. Experiments show that the proposed video synopsis can reduce the spatiotemporal redundancies of the input video as much as possible. Moreover, it can keep the important relationship between objects and maintain the time consistency of important activities.

We present an unusual case of a 41-year-old male patient with a large lymphangioma of the esophagus. Endoscopy revealed that the structure measured 60 × 10 mm in the mucosa and the submucosa and had a heterogenous echo pattern. The esophageal mass was successfully resected by endoscopic piecemeal mucosal resection. However, most esophageal lymphangiomas that are larger than 2 cm in diameter reported in the literature can be removed only through open surgery. Thus far, we know of no reported cases of endoscopic resection as a treatment for this case.

The prevalence of highly infectious influenza A virus (IAV) is still a major threat to global human health. Nitazoxanide (NTZ) possesses potent antiviral properties against the influenza virus. However, the role of small molecular metabolites and antioxidant stress in the NTZ's anti-influenza virus mechanism is not yet fully understood. This study compared the changes in cellular metabolism, ROS levels, antioxidant enzyme activities, and Keap-1/Nrf2 pathway in IAV-infected MDCK cells after NTZ treatment in vitro, using LC-MS-based metabolomics, flow cytometry, immunoblot. We observed that the NTZ treatment in the IAV-infected cells drastically altered the metabolism of small molecules, among which eleven metabolites were highly relevant to NTZ. The virus induced oxidative stress was also remarkably suppressed by NTZ. Meanwhile, the Nrf2 pathway and some proteins with modulating antiviral activity were activated after NTZ treatment, protecting cells from IAV injury. Therefore, regulation of the intracellular oxidative state is the primary outcome of NTZ treatment, which may underpin an antiviral mechanism attributed to the thiazolide. [ABSTRACT FROM AUTHOR]