Environmental pollutants and male infertility: Effects on CatSper.

Infertility is a growing health concern among many couples worldwide. Men account for half of infertility cases. CatSper, a sperm-specific Ca2+ channel, is expressed on the cell membrane of mammalian sperm. CatSper plays an important role in male fertility because it facilitates the entry of Ca2+ necessary for the rapid change in sperm motility, thereby allowing it to navigate the hurdles of the female reproductive tract and successfully locate the egg. Many pollutants present in the environment have been shown to affect the functions of CatSper and sperm, which is a matter of capital importance to understanding and solving male infertility issues. Environmental pollutants can act as partial agonists or inhibitors of CatSper or exhibit a synergistic effect. In this article, we briefly describe the structure, functions, and regulatory mechanisms of CatSper, and discuss the body of literature covering the effects of environmental pollutants on CatSper.

Exposure to polystyrene nanoplastics induces hepatotoxicity involving NRF2-NLRP3 signaling pathway in mice.

Nanoplastic contamination has been of intense concern by virtue of the potential threat to human and ecosystem health. Animal experiments have indicated that exposure to nanoplastics (NPs) can deposit in the liver and contribute to hepatic injury. To explore the mechanisms of hepatotoxicity induced by polystyrene-NPs (PS-NPs), mice and AML-12 hepatocytes were exposed to different dosages of 20 nm PS-NPs in this study. The results illustrated that in vitro and in vivo exposure to PS-NPs triggered excessive production of reactive oxygen species and repressed nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway and its downstream antioxidase expression, thus leading to hepatic oxidative stress. Moreover, PS-NPs elevated the levels of NLRP3, IL-1ß and caspase-1 expression, along with an activation of NF-κB, suggesting that PS-NPs induced hepatocellular inflammatory injury. Nevertheless, the activaton of NRF2 signaling by tert-butylhydroquinone mitigated PS-NPs-caused oxidative stress and inflammation, and inbihited NLRP3 and caspase-1 expression. Conversely, the rescuing effect of NRF2 signal activation was dramatically supressed by treatment with NRF2 inhibitor brusatol. In summary, our results demonstrated that NRF2-NLRP3 pathway is involved in PS-NPs-aroused hepatotoxicity, and the activation of NRF2 signaling can protect against PS-NPs-evoked liver injury. These results provide novel insights into the hepatotoxicity elicited by NPs exposure.

Pyrolysis behavior, kinetics, and thermodynamics of waste pharmaceutical blisters under CO2 atmosphere.

The disastrous impact of COVID-19 pandemic has caused a significantly increased production and use of pharmaceutical drugs, which is accompanied by the rapid generation of waste pharmaceutical blisters (WPBs). Nonetheless, its treatment has not gained appropriate attentions and a perceptible process development was not achieved. In this study, the WPBs pyrolysis in CO2 atmosphere was conducted as well as the thermodynamics and kinetics were investigated. The thermogravimetric analysis revealed that the WPBs decomposition could be divided into two stages of 25 - 365 °C and 365 - 900 °C with mass loss of 56.5 - 60.5 wt% and 22.5 - 25.9 wt%, respectively. Fourier-transform infrared spectroscopy analysis indicated the dechlorination process initiating at ∼300 °C. The simultaneous asymmetric stretching of HCl and stretching vibration of C-Cl bond was detected in the range of 2600 - 3250 cm-1 and 660 - 750 cm-1, respectively. The dechlorination reactions were almost complete at ∼520 °C and minor peaks (2900 -3100 cm-1) due to C-H vibrations were observed. Gas chromatography-mass spectrometry analysis indicated that the evolved products included alkanes, benzene, olefin, as well as HCl. The cycloalkenes content significantly increased during the second conversion stage, implying the addition reactions between alkanes and olefins. The apparent activation energy was calculated using three model-free methods and the values from Flynn-Wall-Ozawa model increased from 142.0 to 255.8 kJ·mol-1 with an average value of 147.4 kJ·mol-1. The methods of Coats-Redfern as well as Malek were applied to determine the reaction mechanism. The one-dimensional diffusion model was more reliable to describe the WPBs pyrolysis. This study will represent a significant reference case for the thermochemical conversion of multilayer packing waste and facing the increasing demand for the medical waste recycling.

Multispectral LiDAR point cloud highlight removal based on color information.

With the rapid development of light detection and ranging (LiDAR) technology, multispectral LiDAR (MSL) can realize three-dimensional (3D) imaging of the ground object by acquiring rich spectral information. Although color restoration has been achieved on the basis of the full-waveform data of MSL, further improvement of the visual effect of color point clouds still faces many challenges. In this paper, a highlight removal method for MSL color point clouds is proposed to explore the potential of 3D visualization. First, the MSL reflection model are introduced according to radar equation and Phong model, and the restored color of the MSL point clouds is determined to comprise diffuse and specular components. Second, a data conversion method is proposed to improve the massive point cloud processing efficiency by spatial dimension reduction and data compression. Then, the visual saliency map after color denoising is used to obtain the highlight region, the unknown information of which is recovered based on the global or local color information. Finally, three representative targets are selected and evaluated by qualitative and quantitative validation, which verifies that the method can effectively recover the high-quality highlight-free point clouds of MSL.

Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy.

The blood-brain barrier (BBB) is the most critical obstacle in the treatment of central nervous system disorders, such as glioma, the most typical type of brain tumor. To overcome the BBB and enhance drug-penetration abilities, we used angiopep-2-modified liposomes to deliver arsenic trioxide (ATO) across the BBB, targeting the glioma. Angiopep-2-modified calcium arsenite-loaded liposomes (A2-PEG-LP@CaAs), with uniformly distributed hydrodynamic diameter (96.75 ± 0.57 nm), were prepared using the acetate gradient method with high drug-loading capacity (7.13 ± 0.72%) and entrapment efficiency (54.30 ± 9.81%). In the acid tumor microenvironment, arsenic was responsively released, thereby exerting an anti-glioma effect. The anti-glioma effect of A2-PEG-LP@CaAs was investigated both in vitro and in vivo. As a result, A2-PEG-LP@CaAs exhibited a potent, targeted anti-glioma effect mediated by the lipoprotein receptor-related (LRP) receptor, which is overexpressed in both the BBB and glioma. Therefore, A2-PEG-LP@CaAs could dramatically promote the anti-glioma effect of ATO, as a promising strategy for glioma therapy.

Lipid/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide/paclitaxel against breast cancer cells.

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.

Borneol-modified tanshinone IIA liposome improves cerebral ischemia reperfusion injury by suppressing NF-κB and ICAM-1 expression.

OBJECTIVE: To investigate the metabolism and brain tissue distribution of borneol-modified tanshinone IIA liposome (BO-TA-Lip) and its effect on NF-κB and ICAM-1 in cerebral ischemia reperfusion rats, thereby exploring the ameliorative mechanism of BO-TA-Lip on ischemic encephalopathy. METHODS: Particle size, entrapment efficiency, drug loading were measured to evaluate the preparation comprehensively. Metabolism and brain tissue distributions in vivo were measured by HPLC, and the pharmacokinetic parameters were calculated. In addition, 24 SD rats were randomly divided into sham, model, STS (sodium tanshinone IIA sulfonate, 30 mg/kg) and BO-TA-Lip groups (44 mg/kg). The middle cerebral artery occlusion (MCAO) rats were constructed with thread embolism method. Neurological deficits were scored using Zea Longa scoring standard. TTC and HE staining were used for the cerebral infarction and histopathological examination, respectively. The protein expression was examined by immunohistochemistry and Western blot. RESULTS: The average particle size, encapsulation efficiency and drug loading of BO-TA-Lip were (135.33 ± 7.25) nm, (85.95 ± 3.20)% and (4.06 ± 0.31)%, respectively. Both in the pharmacokinetic analysis of plasma and brain tissue, in BO-TA-Lip group, the peak concentration and the area under the curve increased, and the clearance rate decreased. The neurological deficit scores and infarct area of the BO-TA-Lip group were significantly lower than that of the model and STS groups. Besides, BO-TA-Lip reduced the protein expression of NF-κB, ICAM-1, IL-1ß, TNF-α and IL-6 in the brain tissue. CONCLUSION: BO-TA-Lip had higher bioavailability and better absorption in brain tissue, and could improve cerebral ischemia reperfusion injury, which might be related to the inhibitory effect of BO-TA-Lip in expression of NF-κB and ICAM-1.

Pazopanib versus sunitinib in Chinese patients with locally advanced or metastatic renal cell carcinoma: pooled subgroup analysis from the randomized, COMPARZ studies.

BACKGROUND: We performed a pooled analysis of the COMPARZ study assessing efficacy and safety of pazopanib versus sunitinib in treatment-naïve Chinese patients with locally advanced and/or metastatic renal cell carcinoma (a/mRCC). METHODS: In the COMPARZ study, patients were randomized (1:1) to receive pazopanib 800 mg once daily (QD) continuously or sunitinib 50 mg QD in 6-week cycles (4 weeks on, 2 weeks off). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), and safety. PFS and ORR were assessed by independent review committee (IRC) and local investigators. RESULTS: Of the 209 Chinese patients (pazopanib, [n = 109] and sunitinib, [n = 100]), 155 (74%) were males and median age was 57 years (range, 18-79). Median PFS was 13.9 months for pazopanib versus 14.3 months for sunitinib per investigator assessment and 8.3 months in both arms per IRC assessment; PFS hazard ratio was 1.17 (investigator) and 0.99 (IRC). Median OS was not reached in pazopanib arm and was 29.5 months in sunitinib arm. ORR was significantly higher in pazopanib arm versus sunitinib arm (investigator: 41% versus 23% [P = 0.0052]; IRC: 35% versus 20% [P = 0.0203]). Pazopanib was generally well tolerated in Chinese patients with a/mRCC. Most frequent AEs in the pazopanib arm were diarrhea and hair color changes whereas the most frequent AEs in the sunitinib arm were decreased platelets, decreased neutrophil count, and thrombocytopenia. CONCLUSION: The results of the pooled analysis were consistent with the overall population in the COMPARZ study, and confirmed similar PFS and OS of pazopanib and sunitinib in the Chinese patients. TRIAL REGISTRATION: clinical trials.gov, NCT00720941 (August 14, 2008) and NCT01147822 (May 19, 2010).

Hyperspectral lidar point cloud segmentation based on geometric and spectral information.

Light detection and ranging (lidar) can record a 3D environment as point clouds, which are unstructured and difficult to process efficiently. Point cloud segmentation is an effective technology to solve this problem and plays a significant role in various applications, such as forestry management and 3D building reconstruction. The spectral information from images could improve the segmentation result, but suffers from the varying illumination conditions and the registration problem. New hyperspectral lidar sensor systems can solve these problems, with the capacity to obtain spectral and geometric information simultaneously. The former segmentation on hyperspectral lidar were mainly based on spectral information. The geometric segmentation method widely used by single wavelength lidar was not employed for hyperspectral lidar yet. This study aims to fill this gap by proposing a hyperspectral lidar segmentation method with three stages. First, Connected-Component Labeling (CCL) using the geometric information is employed for base segmentation. Second, the output components of the first stage are split by the spectral difference using Density-Based Spatial Clustering of Applications with Noise (DBSCAN). Third, the components of the second stage are merged based on the spectral similarity using Spectral Angle Match (SAM). Two indoor experimental scenes were setup for validation. We compared the performance of our mothed with that of the 3D and intensity feature based method. The quantitative analysis indicated that, our proposed method improved the point-weighted score by 19.35% and 18.65% in two experimental scenes, respectively. These results showed that the geometric segmentation method for single wavelength lidar could be combined with the spectral information, and contribute to the more effective hyperspectral lidar point cloud segmentation.

Phylogenetic characteristics of HIV-1 among travelers entering China from Myanmar: A retrospective study.

Due to the open policy of the Chinese government, a large number of Burmese individuals enter China at land ports in Yunnan province for travel or business. However, the situation of HIV-1 infection and its phylogenetic characteristics among these travelers remains unclear, which is a potential threat to public health. From January 2003 to December 2012, a total of 1,961 travelers were detected to be positive for HIV-1 infection at land ports between Myanmar and Yunnan province, China. From 1153 (58.8%) Burmese of them, we randomly collected 489 serum samples for HIV-1 subtype/recombinant analysis. Based on successfully obtained 223 gag-RT sequences, 187 of them were genotyped as 2 subtypes and 3 CRFs. CRF01_AE was showed to be the most prevalent genotype (54.3%), followed by subtypes C (13.5%) and B (10.8%). Notably, CRF07_BC (1.3%) and CRF08_BC (4.0%) were mainly distributed in travelers from Shan state and Kachin (91.7%, 11/12), but was not found in travelers from the capital city of Yangon (0/16). Additionally, there were 36 samples (16.1%) were preliminary determined as unique recombinant forms (URFs). The higher HIV-1 infection among entering travelers from Myanmar and its diverse and complex genotypes distribution suggest this bridge population may facilitate the transmission of HIV-1. It is necessary to have the strict monitoring on this population for prevention of HIV-1 cross-border transmission.

Effects of humic acids derived from lignite and cattle manure on antioxidant enzymatic activities of barley root.

To investigate the effects of humic acids (HAs) on the ability of plants to defend themselves against oxidative stress, barley was hydroponically cultured in the absence and presence of HAs, and the antioxidant enzymatic activities (catalase, superoxide dismutase, ascorbate and glutathione peroxidases) of root tissue were evaluated. Auxin-like structures in HAs, which were extracted from an oxidation product of lignite (LHA) and compost derived from cattle manure (CHA), were identified by pyrolysis-gas chromatography/mass spectrometry (GC/MS) with tetramethylammonium hydroxide. The LHA, which had the lower molecular weight, was more effective in promoting the growth of barley root than CHA. However, the amounts of auxin-like structures in the CHA were much higher than those for LHA. The antioxidant enzymatic activities were initially decreased in the presence of LHA and CHA at the first day after refreshing the culture solution, but were significantly increased on the second day. The CHA sample, which contained relatively high levels of phenolic acids that contained auxin-like structures, was effective in increasing four types of enzymatic activities, while the activities of catalase and ascorbate peroxidase were increased in the presence of LHA, which contains naphthalene derivatives. These results indicate that using HAs as a supplement can be effective in enhancing antioxidation enzymatic activities, while the appearance of the effects is retarded because of the decomposition and release of auxin-like compounds from HAs by organic acids from the plant roots.

Resveratrol reinforces the therapeutic effect of mesenchymal stem cell (MSC)-derived exosomes against renal ischemia‒reperfusion injury (RIRI)-associated fibrosis by suppressing TGF-ß-induced epithelial-mesenchymal transition.

Resveratrol (RSV) has been shown to prevent epithelial-mesenchymal transition (EMT) in different diseases by modulating several signaling pathways, and RSV can prevent EMT by modulating the signaling of the TGF-ß/Smad axis. In the development of renal ischemia‒reperfusion injury (RIRI), RSV and MSC-derived exosomes could ameliorate RIRI via different signaling pathways. In this study, we aimed to investigate the effect of RSV plus MSC-derived exosomes on the prognosis of RIRI. Quantitative real-time polymerase chain reaction (PCR) was performed to measure the expression of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA in TCMK-1 cells and mice under various conditions. HE and Masson staining were used to evaluate kidney injury and fibrosis in mice under various conditions. RSV effectively maintained the TGF-ß- and AA-induced upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in TCMK-1 cells. Moreover, MSC-derived exosomes effectively reinforced the effect of RSV on reducing the TGF-ß- and AA-induced upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in TCMK-1 cells. Furthermore, MSC-derived exosomes enhanced the capability of RSV to maintain the RIRI-induced increases in Cr and BUN, as well as the upregulation of E-CAD, SMA, COL10A1, VMT and MMP-7 mRNA expression in mice. In addition, MSC-derived exosomes enhanced the capability of RSV to decrease RIRI-induced kidney injury and fibrosis in mice. Our findings showed that the administration of MSC-derived exosomes and RSV could suppress the TGF-ß-induced epithelial-mesenchymal transition. This suppressive effect was promoted by the coadministration of MSC-derived exosomes and RSV.

Transcriptome analysis reveals PRKCA as a potential therapeutic target for overcoming cisplatin resistance in lung cancer through ferroptosis.

Cisplatin-based chemotherapy is the current standard care for lung cancer patients; however, drug resistance frequently develops during treatment, thereby limiting therapeutic efficacy.The molecular mechanisms underlying cisplatin resistance remain elusive. In this study, we conducted an analysis of microarray data from the Gene Expression Omnibus (GEO) database under the accession numbers GSE21656, which encompassed expression profiling of cisplatin-resistant H460 (DDP-H460)and the parental cells (H460). Subsequently, we calculated the differentially expressed genes (DEGs) between DDP-H460 and H460. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs demonstrated significant impact on the Rap1, PI3K/AKT and MAPK signaling pathways. Moreover, protein and protein interaction (PPI) network analysis identified PRKCA, DET1, and UBE2N as hub genes that potentially contribute predominantly to cisplatin resistance. Ultimately, PRKCA was selected for validation due to its significant prognostic effect, which predicts unfavorable overall survival and disease-free survival in patients with lung cancer. Network analysis conducted on The Cancer Genome Atlas (TCGA) database revealed a strong gene-level correlation between PRKCA and TP53, CDKN2A, BYR2, TTN, KRAS, and PIK3CA; whereas at the protein level, it exhibited a high correlation with EGFR, Lck, Bcl2, and Syk. The in vitro experiments revealed that PRKCA was upregulated in the cisplatin-resistant A549 cells (DDP-A549), while knockdown of PRKCA increased DDP-A549 apoptosis upon cisplatin treatment. Moreover, we observed that PRKCA knockdown attenuated DDP-A549 proliferation, migration and invasion ability. Western blot analysis demonstrated that PRKCA knockdown downregulated phosphorylation of PI3K expression while upregulated the genes involved in ferroptosis signaling. In summary, our results elucidate the role of PRKCA in acquiring resistance to cisplatin and underscore its potential as a therapeutic target for cisplatin-resistant lung cancer.

Recent Advances in Polymer-Based Biosensors for Food Safety Detection.

The excessive use of pesticides and drugs, coupled with environmental pollution, has resulted in the persistence of contaminants on food. These pollutants tend to accumulate in humans through the food chain, posing a significant threat to human health. Therefore, it is crucial to develop rapid, low-cost, portable, and on-site biosensors for detecting food contaminants. Among various biosensors, polymer-based biosensors have emerged as promising probes for detection of food contaminants in recent years, due to their various functions such as target binding, enrichment, and simple signal reading. This paper aims to discuss the characteristics of five types of food pollutants-heavy metals, pesticide residues, pathogenic bacteria, allergens, and antibiotics-and their adverse effects on human health. Additionally, this paper focuses on the principle of polymer-based biosensors and their latest applications in detecting these five types of food contaminants in actual food samples. Furthermore, this review briefly examines the future prospects and challenges of biosensors for food safety detection. The insights provided in this review will facilitate the development of biosensors for food safety detection.

LAI estimation based on physical model combining airborne LiDAR waveform and Sentinel-2 imagery.

Leaf area index (LAI) is an important biophysical parameter of vegetation and serves as a significant indicator for assessing forest ecosystems. Multi-source remote sensing data enables large-scale and dynamic surface observations, providing effective data for quantifying various indices in forest and evaluating ecosystem changes. However, employing single-source remote sensing spectral or LiDAR waveform data poses limitations for LAI inversion, making the integration of multi-source remote sensing data a trend. Currently, the fusion of active and passive remote sensing data for LAI inversion primarily relies on empirical models, which are mainly constructed based on field measurements and do not provide a good explanation of the fusion mechanism. In this study, we aimed to estimate LAI based on physical model using both spectral imagery and LiDAR waveform, exploring whether data fusion improved the accuracy of LAI inversion. Specifically, based on the physical model geometric-optical and radiative transfer (GORT), a fusion strategy was designed for LAI inversion. To ensure inversion accuracy, we enhanced the data processing by introducing a constraint-based EM waveform decomposition method. Considering the spatial heterogeneity of canopy/ground reflectivity ratio in regional forests, calculation strategy was proposed to improve this parameter in inversion model. The results showed that the constraint-based EM waveform decomposition method improved the decomposition accuracy with an average 12% reduction in RMSE, yielding more accurate waveform energy parameters. The proposed calculation strategy for the canopy/ground reflectivity ratio, considering dynamic variation of parameter, effectively enhanced previous research that relied on a fixed value, thereby improving the inversion accuracy that increasing on the correlation by 5% to 10% and on R2 by 62.5% to 132.1%. Based on the inversion strategy we proposed, data fusion could effectively be used for LAI inversion. The inversion accuracy achieved using both spectral and LiDAR data (correlation=0.81, R2 = 0.65, RMSE=1.01) surpassed that of using spectral data or LiDAR alone. This study provides a new inversion strategy for large-scale and high-precision LAI inversion, supporting the field of LAI research.

Toxic effects of per- and polyfluoroalkyl substances on sperm: Epidemiological and experimental evidence.

As emerging organic contaminants, per- and polyfluoroalkyl substances (PFASs) have aroused worldwide concern due to their environmental persistence, ubiquitous presence, bioaccumulation, and potential toxicity. It has been demonstrated that PFASs can accumulate in human body and cause multiple adverse health outcomes. Notably, PFASs have been detected in the semen of human, posing a potential hazard to male fecundity. This article reviews the evidence about the toxic effects of exposure to PFASs on male reproduction, focusing on the sperm quality. Epidemiological studies showed that PFASs, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were adversely associated with the semen parameters in humans, including sperm count, morphology and motility. Experimental results also confirmed that PFAS exposure led to testicular and epididymal damage, therefore impairing spermatogenesis and sperm quality. The mechanisms of reproductive toxicity of PFASs may be involved in blood-testosterone barrier destruction, testicular apoptosis, testosterone synthesis disorder, and membrane lipid composition alteration, oxidative stress and Ca2+ influx in sperm. In conclusion, this review highlighted the potential threat of exposure to PFASs to human spermatozoa.

Malacoplakia of the bladder combined with infected renal calculi: A case report.

Introduction: The malacoplakia of the bladder is a rare chronic acquired infection- associated granulomatous disease and even less common in combination with urinary stones. Case Presentation: We report the case of a 58-year-old female patient with malacoplakia of the bladder combined with renal calculi. The patient was admitted to the hospital with bilateral low back pain for one month and space-occupying lesions of the bladder for three days. Preoperative imaging suggested space-occupying lesions of the bladder: high probability of bladder cancer. Following the anti-infection treatment, the transurethral electrodesiccation was performed on the space-occupying lesions of the bladder. Pathological examination confirmed the diagnosis of malacoplakia of the bladder. Left-sided percutaneous nephrolithotomy was performed electively to remove the predisposing factors of infection. After the operation, the patient continued to receive anti-infection treatment for two months. The patient had a good prognosis in the six-month follow-up. Conclusions: Malacoplakia of the bladder is easily misdiagnosed as bladder cancer before operation, and the diagnosis depends on pathological diagnosis. Complete removal of urinary calculi, infection and other inducing factors, is beneficial to the treatment of malacoplakia of the bladder.

COVID-19 Related Early Google Search Behavior and Health Communication in the United States: Panel Data Analysis on Health Measures.

The COVID-19 outbreak at the end of December 2019 spread rapidly all around the world. The objective of this study is to investigate and understand the relationship between public health measures and the development of the pandemic through Google search behaviors in the United States. Our collected data includes Google search queries related to COVID-19 from 1 January to 4 April 2020. After using unit root tests (ADF test and PP test) to examine the stationary and a Hausman test to choose a random effect model, a panel data analysis is conducted to investigate the key query terms with the newly added cases. In addition, a full sample regression and two sub-sample regressions are proposed to explain: (1) The changes in COVID-19 cases number are partly related to search variables related to treatments and medical resources, such as ventilators, hospitals, and masks, which correlate positively with the number of new cases. In contrast, regarding public health measures, social distancing, lockdown, stay-at-home, and self-isolation measures were negatively associated with the number of new cases in the US. (2) In mild states, which ranked one to twenty by the average daily new cases from least to most in 50 states, the query terms about public health measures (quarantine, lockdown, and self-isolation) have a significant negative correlation with the number of new cases. However, only the query terms about lockdown and self-isolation are also negatively associated with the number of new cases in serious states (states ranking 31 to 50). Furthermore, public health measures taken by the government during the COVID-19 outbreak are closely related to the situation of controlling the pandemic.

Identification of Survival Risk and Immune-Related Characteristics of Kidney Renal Clear Cell Carcinoma.

Background: Immunity exerts momentous functions in the progression and treatment of kidney renal clear cell carcinoma (KIRC). A better understanding of the relationship between KIRC and immunity may make a great contribution to evaluating the prognosis and immune-related therapeutic response of KIRC. Methods: A series of information such as RNA sequence, clinical data, and tumor mutation burden (TMB) of KIRC patients were downloaded through The Cancer Genome Atlas (TCGA). Next, combining the survival information and gene expression data of TCGA and Gene Expression Omnibus (GEO), we established an immune gene-related prognosis model (IGRPM) and analyzed it. Then we constructed a nomogram which was convenient for clinicians to judge the prognosis of KIRC. Last but not the least, the expressions of some genes used to construct IGRPM in early KIRC, and adjacent normal tissues were verified through real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Perl (strawberry-perl-5.30.0.1-64bit), R software (4.0.3), and GraphPad Prism 7 were used to process the relevant data. Results: The single-sample gene set enrichment analysis (ssGSEA) showed that there were significant differences in StromalScore, ImmuneScore, ESTIMATEScore, TumorPurity, 22 kinds of human immune cells infiltration, and HLA genes expression between high immunity group (Immunity_H) and low immunity group (Immunity_L). The Immunity_H expressed more immune-related genes and enriched more immune-related functions than the Immunity_L. In addition, compared with the low-risk group, the high-risk group had worse survival outcome and higher TMB. Combining IGRPM-based risk characteristic and TMB, we found that low-TMB + low-risk was the most beneficial to the survival outcome of KIRC patients. The risk characteristic based on IGRPM could be used as an independent prognostic factor for KIRC, and the nomogram constructed for evaluating the prognosis of KIRC showed excellent predictive potential. The RT-qPCR results suggested that not all the genes used to construct IGRPM showed differential expression in early KIRC compared with adjacent normal tissues, but all these genes had significant influence on the prognosis of KIRC. Conclusion: These comprehensive immune assessments and survival predictions, integrating multiple aspects of data and clinical information, can provide additional value to the current Tumor Node Metastasis staging system for risk stratification of KIRC and may facilitate the development of KIRC immunotherapy.

HPLC-MS/MS studies of brimonidine in rabbit aqueous humor by microdialysis.

Aim: The pharmacokinetic study of the brimonidine tartrate in situ gel in the anterior chamber of the rabbit eye was studied by microdialysis technique, and samples were analyzed by HPLC-MS/MS. Materials & methods: It was monitored in ESI mode at transition 291.9→212.0 and 296.0→216.0 for brimonidine and internal standard, respectively. Acetonitrile and 0.1% aqueous formic acid (50:50, v/v) were used as the mobile phase at 0.4 ml/min. Results & conclusion: It showed a good linear correlation between 5 and 5000 ng/ml in microdialysis solution, and the inter- and intra-day precision (relative standard deviation) was less than 4.0%. The pharmacokinetic study showed that the AUC(0-t) of in situ gel was 3.5-times than that of eyedrops, which significantly improve the bioavailability of brimonidine.