Spatial distribution and health risks assessment of heavy metals in e-waste dumping sites from Pakistan.

The present study focused on to determine the concentration and health risk of heavy metals (Cu, Pb, Zn, Cd, Hg, Cr) in e-waste contaminated soils collected from different provinces of Pakistan. Further, the impact of heavy metals on soil enzyme activities and microbial community was also investigated. The concentration (mg/kg) of Hg, Zn, Fe, Cu, Pb, Cd, and Cr ranged between 0-0.258, 2.284-6.587, 3.005-40.72, 8.67-36.88, 12.05-35.03, 1.03-2.43, and 33.13-60.05, respectively. The results revealed that Lahore site of Punjab province indicated more concentration of heavy metals as compared to other sites. The level of Cr at all sites whereas Hg at only two sites exceeds the World Health Organization standards (WHO) for soil. Soil enzyme activity exhibited dynamic trend among the sites. Maximum enzyme activity was observed for urease followed by phosphatase and catalase. Contamination factor (Cf), Pollution load index (PLI), and geo-accumulation index (Igeo) results showed that all the sites are highly contaminated with Cu, Cd, and Pb. Hazard index (HI) was less than 1 for children and adults suggesting non-carcinogenic health risk. Principle component analysis results depicted relation among Cr, Fr, catalase, and actinomycetes; Cd, OM, urease, and bacteria, and Pb, Cu, Zn, Hg, and phosphatase, suggesting soil enzymes and microbial community profiles were influenced by e-waste pollution. Therefore, there is a dire need to introduce sustainable e-waste recycling techniques as well as to make stringent e-waste management policies to reduce further environmental contamination.

A Rapid and Accurate UHPLC Method for Determination of Monosaccharides in Polysaccharides of Different Sources of Radix Astragali and Its Immune Activity Analysis.

With the escalating demand for Astragalus polysaccharides products developed from Radix Astragali (RA), the necessity for quality control of polysaccharides in RA has become increasingly urgent. In this study, a specific method for the simultaneous determination of seven monosaccharides in polysaccharides extracted from Radix Astragali (RA) has been developed and validated using ultra-performance liquid chromatography equipped with an ultraviolet detector (UHPLC-UV) for the first time. The 1-phenyl-3-methyl-5-pyrazolone (PMP) derivatizations were separated on a C18 column (Waters ACQUITYTM, Milfor, MA, USA, 1.8 µm, 2.1 × 100 mm) using gradient elution with a binary system of 5 mm ammonium formate (0.1% formic acid)-acetonitrile for 24 min. Additionally, seven monosaccharides showed good linear relationships (R2, 0.9971-0.9995), adequate precision (RSD < 4.21%), and high recoveries (RSD < 4.70%). The established method was used to analyze 109 batches of RA. Results showed that the Astragalus polysaccharides (APSs) mainly consist of mannose (Man), rhamnose (Rha), glucose (Glu), galactose (Gal), arabinose (Ara), xylose (Xyl); and fucose (Fuc); however, their composition was different among RA samples from different growth patterns, species, growth years, and origins, and the growth mode of RA and the age of wild-simulated RA can be accurately distinguished by principal component analysis (PCA). In addition, the immunological activity of APSs were also evaluated jointly by measurement of the NO release with RAW264.7, with the results showing that APSs have a promoting effect on the release of NO and exhibit a significant correlation with Man, Glu, Xyl, and Fuc contents. Accordingly, the new established monosaccharides analytical method and APS-immune activity determination in this study can provide a reference for quality evaluation and the establishment of quality standards for RA.

Implementing age-friendly policies in China: Assessing the impact on older adults' self-rated health.

Using prefecture-level policy documents (2008-2018) and the China Health and Retirement Longitudinal Study (2011-2018), this study used fixed-effects regressions to examine the associations between the maturity of two age-friendly policies, i.e., old age care (OAC) and preferential treatment (PT) policies for older adults, and the self-rated health (SRH) of older adults. We use policy duration and policy density to measure policy maturity. The results showed positive relationships exist between the density of OAC and PT policy and older adults' SRH, whereas long policy duration often relates to lower SRH. Policy duration and policy density work synergistically. Furthermore, heterogeneity analyses indicated that older adults aged over 75 years, male, those with physical or mental impairment, and living in rural areas and in the first- and second-tier cities benefit significantly from denser OAC policy. The SRH of older adults suffering from physical disabilities or mental problems and living in rural areas is positively associated with denser PT policy. From a policy perspective, our findings suggest that age-friendly policies should be updated over time and be place- and characteristic-tailored.

Association Between Dietary Antioxidant Quality Score (DAQS) and All-Cause Mortality in Hypertensive Adults: A Retrospective Cohort Study from the NHANES Database.

This study aimed to explore the association between the dietary antioxidant quality scores (DAQS) and all-cause mortality in hypertensive adults. In this retrospective cohort study, participants aged ≥ 18 years with hypertension were extracted from the National Health and Nutrition Examination Survey (NAHNES) 2007-2018. Outcome was all-cause mortality of hypertensive participants. DAQS was the exposure variable calculated based on the intake of vitamin A, C, E, zinc, selenium, and magnesium. The weighted univariable and multivariable COX proportional hazards regression models were utilized to explore the association between the DAQS and the all-cause mortality in hypertensive patients and were described as hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on different age, gender, diabetes, and cardiovascular disease (CVD) history were further assessed this association. A total of 16,240 participants were finally included in this study. Until 12 December 2019, 2710 (16.69%) all-cause deaths were documented. After adjustment for confounding variables, high DAQS was associated with the lower all-cause mortality (HR = 0.83, 95%CI: 0.72-0.96) in hypertensive patients. Subgroup analyses suggested that the association between DAQS and the all-cause mortality in hypertensive patients remain robust, especially in patients with female (HR = 0.77, 95%CI: 0.63-0.95), aged ≥ 60 years (HR = 0.81, 95%CI: 0.69-0.96). High DAQS was associated with the lower odds of all-cause mortality in adults with hypertension and are a promising intervention to be further explored in hypertensive patients.

Targeting Ferroptosis Promotes Functional Recovery by Mitigating White Matter Injury Following Acute Carbon Monoxide Poisoning.

Survivors experiencing acute carbon monoxide poisoning (ACMP) tend to develop white matter injury (WMI). The mechanism of ACMP-induced WMI remains unclear. Considering the role of ferroptosis in initiating oligodendrocyte damage to deteriorate WMI, exploring therapeutic options to attenuate ferroptosis is a feasible approach to alleviating WMI. Our results indicated that ACMP induced accumulation of iron and reactive oxygen species (ROS) eventually leading to WMI and motor impairment after ACMP. Furthermore, ferrostatin-1 reduced iron and ROS deposition to alleviate ferroptosis, thereafter reducing WMI to promote the recovery of motor function. The nuclear factor erythroid-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway was found to be involved in alleviating ferroptosis as seen with the administration of ferrostatin-1. The present study rationalizes that targeting ferroptosis to alleviate WMI is a feasible therapeutic strategy for managing ACMP.

Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway.

PURPOSE: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. METHODS: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. RESULTS: Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol. CONCLUSIONS: Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Electrochemistry detection of estrogenic effect: Regulation of de novo purine synthesis and catabolism by gibberellin and fulvestrant.

The estrogenic effect of plant growth regulators has been received little attention, which leads to the lack of relevant toxicity data. In this study, the estrogenic effect induced by gibberellin with ERα-dependent manner was found by E-screen and western blot methods, and the electrochemical signals of MCF-7 cells regulated by gibberellin and fulvestrant were investigated. The results showed that the electrochemical signals of MCF-7 cells were increased by gibberellin, while reduced by fulvestrant significantly, and displayed an extremely sensitive response to the effects of estrogenic effect induced by ERα agonist and antagonist. Western blot results showed that the expressions of phosphoribosyl pyrophosphate amidotransferase and hypoxanthine nucleotide dehydrogenase in de novo purine synthesis and adenine deaminase in catabolism were more effective regulated by gibberellin and fulvestrant, resulting in significant changes of the levels of guanine, hypoxanthine and xanthine in cells, and then electrochemical signals. The results provide a theoretical basis for the establishment of new electrochemical detection method of the estrogenic effect of plant regulators.

Isolation and Identification of Chemical Compounds from Agaricus blazei Murrill and Their In Vitro Antifungal Activities.

This study explores the antifungal properties of Agaricus blazei Murrill, a valuable medicinal and edible fungus. Six compounds (1-6) were first isolated from A. blazei using various isolation techniques and identified using spectroscopic methods. These compounds include linoleic acid, 1,1'-oxybis(2,4-di-tert-butylbenzene), glycerol monolinoleate, volemolide (17R)-17-methylincisterol, (24s)-ergosta-7-en-3-ol, and dibutyl phthalate. This study also assesses the antifungal activities of these compounds against Trichophyton mentagrophology, Trichophyton rubrum, Candida albicans, and Cryptococcus neoformans. The results demonstrate varied sensitivities against these pathogenic fungi, with compound 2 showing significant inhibition against T. mentagrophology, compound 3 showing significant inhibition against T. rubrum, and compound 6 showing significant inhibition against C. albicans. This study underscores the medicinal potential of A. blazei as an antifungal agent and sheds light on its valuable research implications.

Classification and Authentication of Lonicerae Japonicae Flos and Lonicerae Flos by Using 1H-NMR Spectroscopy and Chemical Pattern Recognition Analysis.

Lonicerae japonicae flos and Lonicerae flos are increasingly widely used in food and traditional medicine products around the world. Due to their high demand and similar appearance, they are often used in a confused or adulterated way; therefore, a rapid and comprehensive analytical method is highly required. In this case, the comparative analysis of a total of 100 samples with different species, growth modes, and processing methods was carried out by nuclear magnetic resonance (1H-NMR) spectroscopy and chemical pattern recognition analysis. The obtained 1H-NMR spectrums were employed by principal component analysis (PCA), partial least-squares discriminant analysis (PLS-DA), orthogonal partial least-squares discriminant analysis (OPLS-DA), and linear discriminant analysis (LDA). Specifically, after the dimensionality reduction of data, linear discriminant analysis (LDA) exhibited good classification abilities for the species, growth modes, and processing methods. It is worth noting that the sample prediction accuracy from the testing set and the cross-validation predictions of the LDA models were higher than 95.65% and 98.1%, respectively. In addition, the results showed that macranthoidin A, macranthoidin B, and dipsacoside B could be considered as the main differential components of Lonicerae japonicae flos and Lonicerae Flos, while secoxyloganin, secologanoside, and sweroside could be responsible for distinguishing cultivated and wild Lonicerae japonicae Flos. Accordingly, 1H-NMR spectroscopy combined with chemical pattern recognition gives a comprehensive overview and provides new insight into the quality control and evaluation of Lonicerae japonicae flos.

Discrimination of Radix Astragali from Different Growth Patterns, Origins, Species, and Growth Years by an H1-NMR Spectrogram of Polysaccharide Analysis Combined with Chemical Pattern Recognition and Determination of Its Polysaccharide Content and Immunological Activity.

The fraud phenomenon is currently widespread in the traditional Chinese medicine Radix Astragali (RA) market, especially where high-quality RA is substituted with low-quality RA. In this case, focused on polysaccharides from RA, the classification models were established for discrimination of RA from different growth patterns, origins, species, and growth years. 1H Nuclear Magnetic Resonance (H1-NMR) was used to establish the spectroscopy of polysaccharides from RA, which were used to distinguish RA via chemical pattern recognition methods. Specifically, orthogonal partial least squares discriminant analysis (OPLS-DA) and linear discriminant analysis (LDA) were used to successfully establish the classification models for RA from different growth patterns, origins, species, and growth years. The satisfactory parameters and high accuracy of internal and external verification of each model exhibited the reliable and good prediction ability of the developed models. In addition, the polysaccharide content and immunological activity were also tested, which was evaluated by the phagocytic activity of RAW 264.7. And the result showed that growth patterns and origins significantly affected the quality of RA. However, there was no significant difference in the aspects of origins and growth years. Accordingly, the developed strategy combined with chemical information, biological activity, and multivariate statistical method can provide new insight for the quality evaluation of traditional Chinese medicine.

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro-/- female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro-/- female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.

Cryptosporidium parvum hijacks a host's long noncoding RNA U90926 to evade intestinal epithelial cell-autonomous antiparasitic defense.

Cryptosporidium is a zoonotic apicomplexan parasite that infects the gastrointestinal epithelium and other mucosal surfaces in humans. It is an important opportunistic pathogen in AIDS patients and a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. The intestinal epithelial cells provide the first line of defense against Cryptosporidium infection and play a central role in activating and regulating the host's antiparasitic response. Increasing evidence suggests that long noncoding RNAs (lncRNAs) participate in host-pathogen interactions and play a regulatory role in the pathogenesis of diseases but the underlying molecular mechanisms are not fully understood. We previously identified a panel of host lncRNAs that are upregulated in murine intestinal epithelial cells following Cryptosporidium infection, including U90926. We demonstrate here that U90926 is acting in a pro-parasitic manner in regulating intestinal epithelial cell-autonomous antiparasitic defense. Inhibition of U90926 resulted in a decreased infection burden of the parasite while overexpression of U90926 showed an increase in infection burden in cultured murine intestinal epithelial cells. Induction of U90926 suppressed transcription of epithelial defense genes involved in controlling Cryptosporidium infection through epigenetic mechanisms. Specifically, transcription of Aebp1, which encodes the Aebp1 protein, a potent modulator of inflammation and NF-κB signaling, was suppressed by U90926. Gain- or loss-of-function of Aebp1 in the host's epithelial cells caused reciprocal alterations in the infection burden of the parasite. Interestingly, Cryptosporidium carries the Cryptosporidium virus 1 (CSpV1), a double-stranded (ds) RNA virus coding two dsRNA fragments, CSpV1-dsRdRp and CSpV1-dsCA. Both CSpV1-dsRdRp and CSpV1-dsCA can be delivered into infected cells as previously reported. We found that cells transfected with in vitro transcribed CSpV1-dsCA or CSpV1-dsRdRp displayed an increased level of U90926, suggesting that CSpV1 is involved in the upregulation of U90926 during Cryptosporidium infection. Our study highlights a new strategy by Cryptosporidium to hijack a host lncRNA to suppress epithelial cell-autonomous antiparasitic defense and allow for a robust infection.

Can heterogeneous environmental regulations improve industrial green total factor energy efficiency?

Whether heterogeneous environmental regulations in China can improve industrial green total factor energy efficiency (IGTFEE) is essential to sustainable industrial development nationwide. However, under China's fiscal decentralization system, the impact of heterogeneous environmental regulations on the IGTFEE and its underlying mechanism needs further exploration. This study incorporates capital misallocation and local government competition into the research framework and systematically investigates the mechanisms and effects of environmental regulations affecting the IGTFEE under China's fiscal decentralization system. Based on provincial panel data from 2007 to 2020, this study measured the IGTFEE using the Super-SBM model with undesirable outputs. Based on efficiency, this study uses a bidirectional fixed-effects model, an intermediary effect model, and a spatial Durbin model for empirical testing. The results show that the effect of command-and-control environmental regulation on the IGTFEE presents an inverted U shape, while the effect of market-incentive environmental regulation on the IGTFEE presents a U shape. Conversely, the effect of command-and-control environmental regulation on capital misallocation presents a U shape, while the effect of market-incentive environmental regulation on capital misallocation presents an inverted U shape. Capital misallocation is the mediating variable of heterogeneous environmental regulations affecting IGTFEE, but heterogeneous environmental regulations do not affect the IGTFEE through the same mechanisms. The spatial spillover effects of command-and-control and market-incentive environmental regulations on IGTFEE present a U shape. Local governments adopt a differentiation strategy for command-and-control environmental regulation and a simulation strategy for market-incentive environmental regulation. Environmental regulations have spillover effects on the IGTFEE under different competitive strategies, but only the imitation strategy, characterized by the race-to-the-top, can promote local and neighboring IGTFEE. Therefore, we propose the following recommendations: the central government should flexibly adjust the intensity of environmental regulations to maximize the capital allocation effect, set diversified performance assessment indicators to motivate local governments into the healthy competition and reform the modern fiscal system to correct distortions in the behavior of local governments.

Three-dimensional ori-kirigami metamaterials with multistability.

Ori-kirigami structures offer a good avenue for designing mechanical metamaterials due to their unique advantage of being independent of material properties and scale limitations. Recently, the scientific community has been greatly interested in exploiting the complex energy landscape of ori-kirigami structures to construct multistable systems and play their valuable role in different applications. Here, we present three-dimensional ori-kirigami structures based on generalized waterbomb units, a cylindrical ori-kirigami structure based on waterbomb units, and a conical ori-kirigami structure based on trapezoidal waterbomb units. We investigate the inherent relationships between the unique kinematics and mechanical properties of these three-dimensional ori-kirigami structures and explore their potential usage as mechanical metamaterials that exhibit negative stiffness, snap-through, hysteresis effects, and multistability. What makes the structures even more attractive is their massive folding stroke, where the conical ori-kirigami structure can obtain a huge folding stroke of more than twice its initial height through penetration of its upper and lower boundaries. This study forms the foundation for designing and constructing three-dimensional ori-kirigami metamaterials based on generalized waterbomb units for various engineering applications.

Moderate precipitation reduction enhances nitrogen cycling and soil nitrous oxide emissions in a semi-arid grassland.

The ongoing climate change is predicted to induce more weather extremes such as frequent drought and high-intensity precipitation events, causing more severe drying-rewetting cycles in soil. However, it remains largely unknown how these changes will affect soil nitrogen (N)-cycling microbes and the emissions of potent greenhouse gas nitrous oxide (N2 O). Utilizing a field precipitation manipulation in a semi-arid grassland on the Loess Plateau, we examined how precipitation reduction (ca. -30%) influenced soil N2 O and carbon dioxide (CO2 ) emissions in field, and in a complementary lab-incubation with simulated drying-rewetting cycles. Results obtained showed that precipitation reduction stimulated plant root turnover and N-cycling processes, enhancing soil N2 O and CO2 emissions in field, particularly after each rainfall event. Also, high-resolution isotopic analyses revealed that field soil N2 O emissions primarily originated from nitrification process. The incubation experiment further showed that in field soils under precipitation reduction, drying-rewetting stimulated N mineralization and ammonia-oxidizing bacteria in favor of genera Nitrosospira and Nitrosovibrio, increasing nitrification and N2 O emissions. These findings suggest that moderate precipitation reduction, accompanied with changes in drying-rewetting cycles under future precipitation scenarios, may enhance N cycling processes and soil N2 O emissions in semi-arid ecosystems, feeding positively back to the ongoing climate change.

The Effect of Descending Resources Reform on Reallocating Healthcare Resources: An Analysis Based on the Difference-in-Differences Method.

Since 2010, China has been exploring descending resources reform in order to correct the imbalanced allocation of healthcare resources and promote coordinated economic development among regions. This paper for the first time estimates the impact this reform has had on the reallocation of healthcare resources by using prefecture-level cities panel data from Zhejiang Province, China, which implemented the reform province-wide in 2013. The time-varying difference-in-differences (DID) method was used to estimate the reform's policy effects. The data used in this paper is from published statistical yearbooks and local governments, which include panel data from 11 prefecture-level and higher cities in Zhejiang Province as the treated group and 46 prefecture-level cities in Jiangsu, Henan, and Sichuan Province as the control group. The entropy weight method was used to construct the supply index and demand index to incorporate multiple inputs and outputs, and efficiency indicators were constructed using the ratio method. This research found that the reform has had a positive effect on outpatient visits in different prefecture-level cities with vast rural areas. However, this reform exerted no significant impact on inpatient services or supply-side or resource allocation efficiency. Several robust tests support the above conclusions, and one theoretical explanation is provided. The descending health resources reform can be a valuable reform path in promoting more balanced healthcare resource allocation; however, the resultant disparities in its effects should be considered when implementing it.

Gefitinib improves severe bronchorrhea and prolongs the survival of a patient with lung invasive mucinous adenocarcinoma: A case report.

BACKGROUND: Lung invasive mucinous adenocarcinoma (LIMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare disease that usually presents as bilateral lung infiltration, is unsuitable for surgery and radiotherapy, and shows poor response to conventional chemotherapy. CASE SUMMARY: We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia, but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography -guided percutaneous lung biopsy. Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d. After more than 11 months of treatment, there is no evidence of recurrence or severe adverse events. CONCLUSION: Although the precise mechanism of the antitumor effects of gefitinib are not clear, our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.

Kv1.3 Blockade Alleviates White Matter Injury through Reshaping M1/M2 Phenotypes via the NF-κB Signaling Pathway after Intracerebral Hemorrhage.

BACKGROUND: White matter injury (WMI) in basal ganglia usually induces long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel expressed in microglia and induces neuroinflammation after ICH. Here, we investigated the functions and roles of Kv1.3 activation-induced inflammatory response in WMI and the Kv1.3 blockade effect on microglia polarization after ICH. METHODS: Mice ICH model was constructed by autologous blood injection. The expression of Kv1.3 was measured using immunoblot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays. Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a selectively pharmacological Kv1.3 blocker, was investigated using open field test (OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked immunosorbent assay (ELISA) were taken to elucidate the expression of pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1's function in regulating microglia polarization was investigated using immunoblot, RT-qPCR, and immunostaining assays. The downstream PAP-1 signaling pathway was determined by RT-qPCR and immunoblot. RESULTS: Kv1.3 expression was increased in microglia around the hematoma significantly after ICH. PAP-1 markedly improved neurological outcomes and the WMI by reducing pro-inflammatory cytokine accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1 reduces NF-κB p65 and p50 activation, thus facilitating microglia polarization into M2-like microglia, which exerts this beneficial effect. CONCLUSIONS: PAP-1 reduced pro-inflammatory cytokines accumulation and increased anti-inflammatory factors by facilitating M2-like microglia polarization via the NF-κB signaling pathway. Thus, the current study shows that the Kv1.3 blockade is capable of ameliorating WMI by facilitating M2-like phenotype microglia polarization after ICH.

Effect of layer thickness for the bounce of a particle settling through a density transition layer.

We study numerically a spherical particle settling through a density transition layer at moderate Reynolds numbers Re_{u}=69∼259 for the upper fluid. We investigate how the transition layer thickness affects the particle's bouncing behavior as it crosses the interface. The previous intuitive understanding was that the bounce occurs when the relative thickness of the transition layer, L/D, which is characterized by the ratio of the layer thickness L to the particle diameter D, is small. Indeed, we report no bounce phenomenon for very thick interfaces, i.e., L/D>10 in the current parametric range. However, we argue that the bounce can also be inhibited when L/D is too small. Upon a fixed upper layer Reynolds number Re_{u}=207 with varying L/D, we examine the flow evolution of these cases. We propose that this inhibition is attributed to two mechanisms. First, as the interface thickness decreases, the detachment of the attached lighter fluid from the upper layer occurs more rapidly, resulting in a faster decrease in buoyancy. Second, in the case of a very thin interface (L/D=0.5-3.0), the residual light fluid accumulates and undergoes a secondary detachment, separating from the particle at an angle relative to the central axis. This secondary detachment reduces the drag force and effectively prevents the particle from experiencing a rebound motion.