Environmental dose of 16 priority-controlled PAHs induce endothelial dysfunction: An in vivo and in vitro study.

Polycyclic aromatic hydrocarbons (PAHs) exposure is related to the occurrence of cardiovascular diseases (CVDs). Endothelial dysfunction is considered an initial event of CVDs. To confirm the relationship of PAHs exposure with endothelial dysfunction, 8-week-old male SD rats and primary human umbilical vein endothelial cells (HUVECs) were co-treated with environmental doses of 16 priority-controlled PAHs for 90 d and 48 h, respectively. Results showed that 10× PAHs exposure remarkably raised tumor necrosis factor-α and malonaldehyde levels in rat serum (p < 0.05), but had no effects on interleukin-8 levels and superoxide dismutase activity. The expressions of SIRT1 in HUVECs and rat aorta were attenuated after PAHs treatment. Interestingly, PAHs exposure did not activate the expression of total endothelial nitric oxide synthase (eNOS), but 10× PAHs exposure significantly elevated the expression of phosphorylated eNOS (Ser1177) in HUVECs and repressed it in aortas, accompanied with raised nitrite level both in serum and HUVECs by 48.50-253.70 %. PAHs exposure also led to the augment of endothelin-1 (ET-1) levels by 19.76-38.54 %, angiotensin (Ang II) levels by 20.09-39.69 % in HUVECs, but had no effects on ET-1 and Ang II levels in serum. Additionally, PAHs exposure improved endocan levels both in HUVECs and serum by 305.05-620.48 % and stimulated the THP-1 cells adhered to HUVECs (p < 0.05). After PAHs treatment, the smooth muscle alignment was disordered and the vascular smooth muscle locally proliferated in rat aorta. Notably, the systolic blood pressure of rats exposed to 10× PAHs increased significantly compared with the control ones (131.28 ± 5.20 vs 116.75 ± 5.33 mmHg). In summary, environmental chronic PAHs exposure may result in endothelial dysfunction in SD rats and primary HUVECs. Our research can confirm the cardiovascular damage caused by chronic exposure to PAHs and provide ideas for the prevention or intervention of CVDs affected by environmental factors.

Cross-reactive antibody response to Monkeypox virus surface proteins in a small proportion of individuals with and without Chinese smallpox vaccination history.

BACKGROUND: After the eradication of smallpox in China in 1979, vaccination with the vaccinia virus (VACV) Tiantan strain for the general population was stopped in 1980. As the monkeypox virus (MPXV) is rapidly spreading in the world, we would like to investigate whether the individuals with historic VACV Tiantan strain vaccination, even after more than 40 years, could still provide ELISA reactivity and neutralizing protection; and whether the unvaccinated individuals have no antibody reactivity against MPXV at all. RESULTS: We established serologic ELISA to measure the serum anti-MPXV titer by using immunodominant MPXV surface proteins, A35R, B6R, A29L, and M1R. A small proportion of individuals (born before 1980) with historic VACV Tiantan strain vaccination exhibited serum ELISA cross-reactivity against these MPXV surface proteins. Consistently, these donors also showed ELISA seropositivity and serum neutralization against VACV Tiantan strain. However, surprisingly, some unvaccinated young adults (born after 1980) also showed potent serum ELISA activity against MPXV proteins, possibly due to their past infection by some self-limiting Orthopoxvirus (OPXV). CONCLUSIONS: We report the serum ELISA cross-reactivity against MPXV surface protein in a small proportion of individuals both with and without VACV Tiantan strain vaccination history. Combined with our serum neutralization assay against VACV and the recent literature about mice vaccinated with VACV Tiantan strain, our study confirmed the anti-MPXV cross-reactivity and cross-neutralization of smallpox vaccine using VACV Tiantan strain. Therefore, it is necessary to restart the smallpox vaccination program in high risk populations.

Sequential inspiratory muscle exercise-noninvasive positive pressure ventilation alleviates oxidative stress in COPD by mediating SOCS5/JAK2/STAT3 pathway.

BACKGROUND: Pulmonary rehabilitation training is of great significance for the prognosis of chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to investigate the therapeutic effect and pathway of a new sequential noninvasive positive pressure ventilation (NIPPV) + inspiratory muscle training (IMT) therapy. METHODS: A total of 100 COPD patients were enrolled and randomly divided into oxygen therapy (OT), NIPPV, IMT and sequential (NIPPV + IMT) group. Lung function, exercise endurance, quality of life, and dyspnea symptoms were examined and recorded. Then, reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) levels were detected by enzyme-linked immunoassay, and suppressor of cytokine signaling 5 (SOCS5)/janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway expression changes were detected by quantitative real time-polymerase chain reaction (qRT-PCR) and western blot. A mouse model of COPD was then established to further verify the effects of SOCS5/JAK2/STAT3 pathways on lung function and oxidative stress. RESULTS: After 8 weeks of treatment, NIPPV, IMT or sequential (NIPPV + IMT) significantly improved exercise endurance, quality of life and dyspnea, reduced oxidative stress, promoted SOCS5 expression and inhibited the activation of JAK2/STAT3 pathway, and no significant effect was observed on lung function of COPD patients. Notably, sequential (NIPPV + IMT) showed better therapeutic outcomes than either IMT or NIPPV alone. Moreover, results at the animal level showed that overexpression of SOCS5 significantly reduced pulmonary inflammatory infiltration, pathological changes and oxidative stress levels in COPD mice, enhanced lung function, and inhibited the activation of JAK2/STAT3 pathway. CONCLUSION: Our results elucidated that sequential (NIPPV + IMT) significantly relieved COPD development by regulating SOCS5/JAK2/STAT3 signaling-mediated oxidative stress.

Visible-Light-Promoted Regioselective Hydroborylation of Ketene Dithioacetals with NHC-Boranes.

NHC-boranes have been treated as a reliable source of boryl radicals. In this study, regioselective hydroborylation of ketene dithioacetals with NHC-borane was achieved under mild conditions via a visible-light-promoted radical chain process using thiophenol as a proton donor and hydrogen atom transfer. This protocol features a low-cost catalyst, good functional group tolerance, a relatively broad range of substrate scope, and good to excellent yields. Moreover, mechanism of this hydroborylation reaction was preliminarily studied.

Upregulated Mitochondrial Dynamics Is Responsible for the Procatabolic Changes of Chondrocyte Induced by α2-Adrenergic Signal Activation.

OBJECTIVE: Activation of sympathetic tone is important for cartilage degradation in osteoarthritis (OA). Recent studies reported that sympathetic signals can affect the mitochondrial function of target cells. It is unknown whether this effect exits in chondrocytes and affects chondrocyte catabolism. The contribution of mitochondrial dynamics in the activation of α2-adrenergic signal-mediated chondrocyte catabolism was investigated in this study. DESIGN: Primary chondrocytes were stimulated with norepinephrine (NE) alone, or pretreated with an α2-adrenergic receptor (Adra2) antagonist (yohimbine) and followed by stimulation with NE. Changes in chondrocyte metabolism and their mitochondrial dynamics were investigated. RESULTS: We demonstrated that NE stimulation induced increased gene and protein expressions of matrix metalloproteinase-3 and decreased level of aggrecan by chondrocytes. This was accompanied by upregulated mitochondriogenesis and the number of mitochondria, when compared with the vehicle-treated controls. Mitochondrial fusion and fission, and mitophagy also increased significantly in response to NE stimulation. Inhibition of Adra2 attenuated chondrocyte catabolism and mitochondrial dynamics induced by NE. CONCLUSIONS: The present findings indicate that upregulation of mitochondrial dynamics through mitochondriogenesis, fusion, fission, and mitophagy is responsible for activation of α2-adrenergic signal-mediated chondrocyte catabolism. The hypothesis that "α2-adrenergic signal activation promotes cartilage degeneration in temporomandibular joint osteoarthritis (TMJ-OA) by upregulating mitochondrial dynamics in chondrocytes" is validated. This represents a new regulatory mechanism in the chondrocytes of TMJ-OA that inhibits abnormal activation of mitochondrial fusion and fission is a potential regulator for improving mitochondrial function and inhibiting chondrocyte injury and contrives a potentially innovative therapeutic direction for the prevention of TMJ-OA.

Differentiated Fractionation of Various Biomass Resources by p-Toluenesulfonic Acid at Mild Conditions.

Biomass is the ideal substitute for petrochemical resources because of its renewable and abundant sources. p-Toluenesulfonic acid (p-TsOH) can effectively separate lignin from biomass under mild conditions, so it is highly expected in biomass fractionation to improve the utilization efficiency. In this study, we investigated the effect of p-TsOH differentiated fractionation of poplar sawdust, eucalyptus sawdust, and rice straw below 100 °C. According to the experimental results, upon pretreatment by p-TsOH of the three kinds of raw biomass, most of the lignin and hemicellulose of poplar sawdust and eucalyptus sawdust were removed, whereas the cellulose was retained, but most of the hemicellulose and cellulose of rice straw were kept, whereas the lignin was removed at similar conditions. The structures and compositions of pretreatment residues, lignin, and hemicellulose extracted from raw biomass were characterized by XRD, FTIR, HSQC-NMR, XPS, and SEM. The differentiated fractionation mechanism of biomass was analyzed. A better recognition and understanding of the factors affecting biomatrix opening and fractionation will allow for the identification of new pretreatment strategies that improve biomass utilization and permit the rational enzymatic hydrolysis of cellulose.

Fortuitous somatic mutations during antibody evolution endow broad neutralization against SARS-CoV-2 Omicron variants.

Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.

Bioactive semaphorin 3A promotes sequential formation of sensory nerve and type H vessels during in situ osteogenesis.

Introduction: Sensory nerves and vessels are critical for skeletal development and regeneration, but crosstalk between neurovascular network and mineralization are not clear. The aim of this study was to explore neurovascular changes and identify bioactive regulators during in situ osteogenesis. Method: In situ osteogenesis model was performed in male rats following Achilles tenotomy. At 3, 6 and 9 weeks after surgery, mineralization, blood vessels, sensory innervation, and bioactive regulators expression were evaluated via micro-computed tomography, immunofluorescent staining, histology and reverse transcriptase-polymerase chain reaction analyses. Result: In the process of in situ osteogenesis, the mineral density increased with time, and the locations of minerals, nerves and blood vessels were highly correlated at each time point. The highest density of sensory nerve was observed in the experimental group at the 3rd week, and then gradually decreased with time, but still higher than that in the sham control group. Among many regulatory factors, semaphorin 3A (Sema3A) was highly expressed in experimental model and its expression was temporally sequential and spatially correlated sensory nerve. Conclusion: The present study showes that during in situ osteogenesis, innervation and angiogenesis are highly correlated, and Sema3A is associated with the position and expression of the sensory nerve.

Black odorous water concentrating by forward osmosis: rejection performance of characteristic pollutants based on cation exchange.

This study aimed to investigate pollutant concentration and nitrogen interception characteristics of a forward osmosis (FO) process for concentrating black odorous water. The membrane cell was operated in active layer facing feed solution (AL-FS) mode with aquaporin (AQP) as the membrane material and NaCl solution as the draw solution (DS). The organic pollutants (COD), TP, NH+4-N, NO-3-N, TN, Fe and Mn in black odorous water were concentrated non-intermittently for 24 h, and their interception characteristics were investigated. The results showed that the average interception rates of COD, TP, NO- 3-N, TN, Fe and Mn were 97.2%, 98.0%, 58.7%, 54.3%, 61.8% and 60.0%, respectively, while the average interception rate of NH+4-N was only 1.27%-3.47%. To explore the characteristics of nitrogen interception, a comparison was conducted between AQP membrane and thin film composite (TFC) membrane. Because the surface electronegativity of AQP membrane was stronger than that of TFC, the effect of cation exchange on ammonia nitrogen interception was more serious with AQP membrane. With NaCl solution as DS, the reverse osmosis flux of Na+ was (0.53 ± 0.02 mol·m-2·h-1), which was significantly higher than that of Cl- (0.29 ± 0.03 mol·m-2·h-1) (P < 0.05). The interception effect of AQP membrane on TN was related to the proportion of NH+4-N in TN. The pretreatment of black odorous water by aeration could transform part of NH+4-N into NO-3-N, and reduce the negative effect of cation exchange effect on nitrogen interception. The TN interception rate increased from 54.3% to 66.1%.

Efficacy of cognitive behavioural therapy for insomnia or sleep disturbance in pregnant women: A systematic review ad meta-analysis.

During pregnancy many women may experience negative emotions and sleep disturbances. This systematic review and meta-analysis was conducted to assess the efficacy of cognitive behavioural therapy for insomnia (CBT-I) or sleep disturbance in pregnant women. From the earliest available publications to 15 April 2022, seven electronic literature databases were searched: PubMed, Web of Science, Cochrane Library, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Database for Chinese Science and Technology Journal. Randomised controlled trials of CBT-I in pregnant women with insomnia or sleep disorders were included. The methodological bias of the included studies was assessed using the Cochrane risk of bias tool. The meta-analysis was performed using RevMan 5.4 software. Stata Statistical Software: Release 15 was used for sensitivity analysis and publication bias. We included eight randomised controlled trials involving 743 pregnant women. Meta-analysis showed that, compared with the control group, CBT-I significantly improved the Insomnia Severity Index (mean difference [MD] = -4.25, 95% confidence interval [CI, -6.32, -2.19], p < 0.001), The Pittsburgh Sleep Quality Index (MD = -3.30, 95% CI [-4.81, -1.79], p < 0.001), sleep onset latency (standardised mean difference [SMD] = -1.25, 95% CI [-2.01, -0.50], p = 0.001), anxiety (SMD = -0.99, 95% CI [-1.32, -0.67], p < 0.001), and depression (SMD = -0.40, 95% CI [-0.72, -0.07], p = 0.02). No significant differences were found in total sleep time (SMD = 0.31, 95% CI [-0.54, 1.17], p = 0.47) and sleep efficiency (SMD = 0.80, 95% CI [-0.53, 2.13], p = 0.24). CBT-I significantly improved pregnant women's sleep quality, insomnia severity, depression, and anxiety. This meta-analysis provides evidence that CBT-I is valid for insomnia or sleep disturbances during pregnancy.

Characterization of cross-reactive monoclonal antibodies against SARS-CoV-1 and SARS-CoV-2: Implication for rational design and development of pan-sarbecovirus vaccines and neutralizing antibodies.

Emergence of various circulating SARS-CoV-2 variants of concern (VOCs) promotes the identification of pan-sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross-reactive against both SARS-CoV-1 and SARS-CoV-2 and to search the criterion for bNAbs against all emerging SARS-CoV-2, we isolated several SARS-CoV-1-cross-reactive monoclonal antibodies (mAbs) from a wildtype SARS-CoV-2 convalescent donor. These antibodies showed broad binding capacity and cross-neutralizing potency against various SARS-CoV-2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross-reactive against SARS-CoV-1 through their escape mutations. Further evaluation of a series of SARS-CoV-1/2-cross-reactive bNAbs showed a negative correlation between the neutralizing activities against SARS-CoV-1 and SARS-CoV-2 Omicron variant. Together, these results suggest the necessity of using cross-neutralization against SARS-CoV-1 and SARS-CoV-2 Omicron as criteria for rational design and development of potent pan-sarbecovirus vaccines and bNAbs.

Standing in customers' shoes: How responsible leadership inhibits unethical pro-organizational behavior.

Although the negative impact of responsible leadership on employees' unethical pro-organizational behavior has been documented in the literature, little is known about its underlying processes and boundaries. Drawing on social information processing theory and social learning theory, we built a moderated mediation model to explain why and when unethical pro-organizational behavior could be inhibited by responsible leadership. We conducted a two-phase questionnaire survey to collect data. The empirical results based on the sample of 557 Chinese salespeople showed that customer-oriented perspective taking partially mediated the negative link between responsible leadership and unethical pro-organizational behavior and that leader competence strengthened the direct effects of responsible leadership on customer-oriented perspective taking and unethical pro-organizational behavior as well as the indirect effect of responsible leadership on unethical pro-organizational behavior via customer-oriented perspective taking. These findings enrich the current understanding of how responsible leadership relates to unethical pro-organizational behavior, extend the limited literature on customer-oriented perspective taking, and offer some suggestions that managers can follow to inhibit unethical pro-organizational behavior. Limitations and future research directions are also discussed.

Fortuitous Somatic Mutations during Antibody Evolution Endow Broad Neutralization against SARS-CoV-2 Omicron Variants.

Striking antibody evasion by emerging circulating SARS-CoV-2 variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identified a clonally-related antibody family from a convalescent individual. One of the members, XG005, exhibited potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members showed significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface revealed how crucial somatic mutations endowed XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality, exhibited a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provided a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.

[The characteristics of vestibular-evoked myogenic potentials in unilateral Meniere's disease patients at different clinical stages].

Objective:This study was to retrospectively analyze the results of vestibular-evoked myogenic potentials（VEMP） in unilateral Meniere's disease（MD） patients. Methods:The clinical assessment results of MD patients who visited the department between January 2016 to February 2022 were reviewed. Unilateral MD patients who met the inclusion and exclusion criteria were divided into three groups according to clinical stages, namely, group 1（stage Ⅰ+ stage Ⅱ）, group 2（stage Ⅲ） and group 3（stage Ⅳ）. The normal value data were used to investigate the incidence of abnormal P1 and N1 latencies, abnormal P1-N1 interwave latency, and abnormal interaural amplitude asymmetry ratio（IAR）. Afterwards, considering all the above mentioned parameters, the VEMP result of each patient was graded into four levels（grade 1 means VEMP result is normal, grade 2, 3 and 4 means the VEMP result is abnormal in different degrees）. The correlation between VEMP result level and pure tone average（PTA） of MD patients in different clinical stages was examined. Results:The prevalence of cVEMP in three groups was 84.2%, 70.0% and 33.3%, respectively（P<0.05）. The prevalence of oVEMP in three groups was 63.2%, 34.0% and 16.7%, respectively（P<0.05）. The incidence of abnormal P1 latency, N1 letancy and P1-N1 interwave latency of cVEMP was 21.1%, 26.3% and 24.6%, respectively. The incidence of abnormal P1 latency, N1 latency and interwave latency of oVEMP was 15.6%, 43.8% and 3.1%, respectively. The incidence of abnormal cVEMP IAR in group 1, group 2 and group 3 was 6.7%, 21.2% and 33.3%, respectively（P>0.05）. The incidence of abnormal IAR of oVEMP in group 1, group 2 and group 3 was 16.7%, 23.1% and 0, respectively（P>0.05）. cVEMP and oVEMP result levels were significantly correlated with PTA（r=0.339, P<0.01; r=0.362, P<0.01 ）, respectively. Conclusion:With the progression of MD, the function of saccule-vestibular inferior nerve pathway and utricle-vestibular superior nerve pathway would deteriorate in the same way as hearing.

Temporal and Spatial Variation and Driving Forces of Soil Erosion on the Loess Plateau before and after the Implementation of the Grain-for-Green Project: A Case Study in the Yanhe River Basin, China.

To curb soil erosion, the Grain-for-Green Project has been implemented in the Loess Plateau region, and there have been few quantitative evaluations of the impact of ecological engineering on the spatial distribution of soil erosion on the Loess Plateau. In this paper, we used ArcGIS software, the Revised Universal Soil Loss Equation (RUSLE) model and the Geographic Detector (GeoDetector) model to investigate the changes in the spatial distribution of soil erosion and driving forces before and after the implementation of the Grain-for-Green Project in Yanhe River Basin, a typical area on the Loess Plateau. After the implementation of the Grain-for-Green Project, the soil erosion showed a decreasing trend over time and from local improvement to global optimization in space. The implementation of the Grain-for-Green Project led to changes in the dominant driving force of the spatial distribution of soil erosion, with the dominant driving force changing from the slope factor to the vegetation coverage factor. The main driving force of the two-factor interaction on soil erosion spatial differentiation changed from the slope factor and other factors to the vegetation coverage and other factors. The Grain-for-Green Project mainly influenced soil erosion by increasing the vegetation cover. The effect of the Grain-for-Green Project on the spatial distribution of soil erosion had hysteresis and spatial differences, and the direct and indirect driving forces generated by ecological engineering reached more than 50% on average.

eEF2K promotes PD-L1 stabilization through inactivating GSK3ß in melanoma.

BACKGROUND: Immune checkpoint blockade (ICB) targeting programmed death ligand-1 (PD-L1)/programmed cell death protein-1 (PD-1) pathway has become an attractive strategy for cancer treatment; however, unsatisfactory efficacy has limited its clinical benefits. Therefore, a more comprehensive understanding of the regulation of PD-L1 expression is essential for developing more effective cancer immunotherapy. Recent studies have revealed the important roles of eukaryotic elongation factor 2 kinase (eEF2K) in promoting epithelial-mesenchymal transition (EMT), angiogenesis, tumor cell migration and invasion; nevertheless, the exact role of eEF2K in the regulation of tumor immune microenvironment (TIME) remains largely unknown. METHODS: In this study, we used a cohort of 38 patients with melanoma who received anti-PD-1 treatment to explore the association between eEF2K expression and immunotherapy efficacy against melanoma. Immunoprecipitation-mass spectrometry analysis and in vitro assays were used to examine the role and molecular mechanism of eEF2K in regulating PD-L1 expression. We also determined the effects of eEF2K on tumor growth and cytotoxicity of CD8+ T cells in TIME in a mouse melanoma model. We further investigated the efficacy of the eEF2K inhibition in combination with anti-PD-1 treatment in vivo. RESULTS: High eEF2K expression is correlated with better therapeutic response and longer survival in patients with melanoma treated with PD-1 monoclonal antibody (mAb). Moreover, eEF2K protein expression is positively correlated with PD-L1 protein expression. Mechanistically, eEF2K directly bound to and inactivated glycogen synthase kinase 3 beta (GSK3ß) by phosphorylating it at serine 9 (S9), leading to PD-L1 protein stabilization and upregulation, and subsequently tumor immune evasion. Knockdown of eEF2K decreased PD-L1 expression and enhanced CD8+ T cell activity, thus dramatically attenuating murine B16F10 melanoma growth in vivo. Clinically, p-GSK3ß/S9 expression is positively correlated with the expressions of eEF2K and PD-L1, and the response to anti-PD-1 immunotherapy. Furthermore, eEF2K inhibitor, NH125 treatment or eEF2K knockdown enhanced the efficacy of PD-1 mAb therapy in a melanoma mouse model. CONCLUSIONS: Our results suggest that eEF2K may serve as a biomarker for predicting therapeutic response and prognosis in patients receiving anti-PD-1 therapy, reveal a vital role of eEF2K in regulating TIME by controlling PD-L1 expression and provide a potential combination therapeutic strategy of eEF2K inhibition with ICB therapy.

Environmental dose of 16 priority-controlled PAHs mixture induce damages of vascular endothelial cells involved in oxidative stress and inflammation.

Epidemiological studies have shown that cardiovascular diseases caused by PM2.5 pollution account for the second death rate in China. Polycyclic aromatic hydrocarbons (PAHs) are one important group of persistent organic pollutants absorbed on PM2.5. Though individual PAH is related to vascular disease, the relationship between environmental PAHs exposure and vascular damages is still unclear. To explore the effect of PAHs on blood vessel, human umbilical vein endothelial cells (HUVECs) are treated with 16 priority-controlled PAHs at various concentrations to study their cytotoxicity and morphological alteration. Results showed that, after 48 h treatment, PAHs mixture generally attenuated the ability of wound healing, transwell migration and tube formation of HUVECs (p < 0.01) except for 1 × PAHs in transwell migration. Moreover, PAHs increased the levels of ROS and 8-hydroxy-2'-deoxyguanosine (p < 0.05), indicating that it exceeded the scavenging ability of superoxide dismutase activity. However, PAHs mixture did not increase apoptosis rate, which may be attribute to the difference of PAH concentration and composition between this study and previous reports. Downstream signaling cascades significantly and generally upregulated the relative expression of proteins in Nrf2/HO-1 and NF-ƙB/TNF-α pathway with the activation of oxidative stress, including HO-, TNF-α and Nrf2. In summary, this study suggests that environmental mixture of 16 priority-controlled PAHs can induce the damages of vascular endothelial cells involved in cellular oxidative stress and inflammation.

Can leader self-sacrificial behavior inhibit unethical pro-family behavior? A personal identification perspective.

As a kind of deviant and unethical behavior in the workplace, unethical pro-family behavior (UPFB) has recently received increased attention. Yet, the question of how to reduce UPFB remains less well understood. From the personal identification perspective, we hypothesize that leader self-sacrificial behavior (LSSB) inhibits employees' UPFB through the mediation of identification with the leader. We further argue that employees' perceived insider status enhances this hypothesized relationship. Our analysis of two-wave data collected from 236 Chinese employees indicated that identification with the leader partially mediated the negative relationship between LSSB and UPFB. Moreover, the effect of LSSB on identification with the leader and the aforementioned mediating relationship were stronger for employees who perceived themselves as insiders than outsiders. These findings provide theoretical implications for research on UPFB and LSSB and offer some suggestions that managers can follow to inhibit UPFB. Limitations and future research directions are also discussed.

Iridium/f-diaphos catalyzed asymmetric hydrogenation of 2-imidazolyl aryl/alkyl ketones.

The iridium/f-diaphos L1, L5 or L12 catalyzed asymmetric hydrogenation of 2-imidazolyl aryl/alkyl ketones to afford two enantiomers of the desired chiral alcohols with high conversions (up to 99% yield) and moderate to excellent enantioselectivities (61% - >99% ee) was realized for the first time. This protocol could be easily conducted on a gram-scale with a TON of 9700.

A Disease Control-Oriented Land Cover Land Use Map for Myanmar.

Malaria is a serious infectious disease that leads to massive casualties globally. Myanmar is a key battleground for the global fight against malaria because it is where the emergence of drug-resistant malaria parasites has been documented. Controlling the spread of malaria in Myanmar thus carries global significance, because the failure to do so would lead to devastating consequences in vast areas where malaria is prevalent in tropical/subtropical regions around the world. Thanks to its wide and consistent spatial coverage, remote sensing has become increasingly used in the public health domain. Specifically, remote sensing-based land cover/land use (LCLU) maps present a powerful tool that provides critical information on population distribution and on the potential human-vector interactions interfaces on a large spatial scale. Here, we present a 30-meter LCLU map that was created specifically for the malaria control and eradication efforts in Myanmar. This bottom-up approach can be modified and customized to other vector-borne infectious diseases in Myanmar or other Southeastern Asian countries.