Discovery of Novel Antitumor Small-Molecule Agent with Dual Action of CDK2/p-RB and MDM2/p53.

Cell cycle-dependent kinase 2 (CDK2) is located downstream of CDK4/6 in the cell cycle and regulates cell entry into S-phase by binding to Cyclin E and hyper-phosphorylating Rb. Proto-oncogene murine double minute 2 (MDM2) is a key negative regulator of p53, which is highly expressed in tumors and plays an important role in tumorigenesis and progression. In this study, we identified a dual inhibitor of CDK2 and MDM2, III-13, which had good selectivity for inhibiting CDK2 activity and significantly reduced MDM2 expression. In vitro results showed that III-13 inhibited proliferation of a wide range of tumor cells, regardless of whether Cyclin E1 (CCNE1) was overexpressed or not. The results of in vivo experiments showed that III-13 significantly inhibited proliferation of tumor cells and did not affect body weight of mice. The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation.

Hemodynamic study on the therapeutic effects of varying diameter embolic coils in the treatment of intracranial aneurysms.

Endovascular coiling is the predominant method for treating cerebral aneurysms. Extensive reports on selecting coil length, hardness, and material are available. However, the impact of coil diameter on postoperative outcomes remains unclear. This study enrolled six personalized geometric models of intracranial aneurysms: three bifurcation aneurysms and three sidewall aneurysms. Four coil models were constructed by changing the coil diameter. Coil embolization was simulated using the finite element method. Computational fluid dynamics was used to characterize hemodynamics in the aneurysms after embolization. Evaluation parameters included velocity reduction, wall shear stress (WSS), low WSS (LWSS), oscillatory shear index (OSI), relative residence time (RRT), and residual flow volume in the aneurysms. At the peak time (t = 0.17 s), the proportion of LWSS area in bifurcation aneurysms increase with the rise in coil diameter: 0.8D, 71.28 ± 12.62% versus 1D, 74.97 ± 19.17% versus 1.2D, 78.88 ± 18.56% versus 1.4D, 84.00 ± 11.53% (mean ± SD). The proportion of high OSI area decreases as the coil diameter increases: 0.8D, 4.41% ± 2.82% versus 1.0D, 3.78 ± 3.33% versus 1.2D, 2.28% ± 1.77% versus 1.4D, 1.58% ± 1.11% (mean ± SD). The proportion of high RRT area increases as the coil diameter rises: 0.8D, 3.40% ± 1.68% versus 1.0D, 7.67 ± 4.12% versus 1.2D, 9.84% ± 9.50% versus 1.4D, 22.29% ± 14.28% (mean ± SD). Side wall aneurysms do not exhibit the aforementioned trend. Bifurcation aneurysms plugged with a coil of 1.4 times the diameter have the largest RFVs (<10 mm/s) within the group. Aforementioned patterns are not found in sidewall aneurysms. In the treatment of aneurysms with coiling, varying coil diameters can result in different hemodynamic environments within the aneurysm. Larger coil diameters have improved hemodynamic performance for bifurcation aneurysms. However, coil diameter and embolization effectiveness have no significant relationship for sidewall aneurysms.

Coagulation/co-catalytic membrane integrated system for fouling-resistant and efficient water purification.

Low-pressure catalytic membranes allow efficient rejection of particulates and simultaneously removing organics pollutant in water, but the accumulation of dissolved organic matters (DOM) on membrane surface, which cover the catalytic sites and cause membrane fouling, challenges their stable operation in practical wastewater treatment. Here we propose a ferric salt-based coagulation/co-catalytic membrane integrated system that can effectively mitigate the detrimental effects of DOM. Ferric salt (Fe3+) serving both as a DOM coagulant to lower the membrane fouling and as a co-catalyst with the membrane-embedded MoS2 nanosheets to drive perxymonosulfate (PMS) activation and pollutant degradation. The membrane functionalized with 2H-phased MoS2 nanosheets showed improved hydrophilicity and fouling resistance relative to the blank polysulfone membrane. Attributed to the DOM coagulation and co-catalytic generation of surface-bound radicals for decontamination at membrane surface, the catalytic membrane/PMS/ Fe3+ system showed much less membrane fouling and 2.6 times higher pollutant degradation rate in wastewater treatment than the catalytic membrane alone. Our work imply a great potential of coagulation/co-catalytic membrane integrated system for water purification application.

Increased Impact of Aviation on Air Quality and Human Health in China.

China's civil aviation market has rapidly expanded, becoming the world's second-largest. However, the air quality and health impacts caused by its aircraft emissions have been inadequately assessed. Here, we leverage an updated emission inventory of air pollutants with improved temporal and spatial resolution based on hundreds of thousands of flight trajectories and simulate aviation-attributable contributions to ground-level air pollution in China. We find that in 2017, the annual-average aviation-attributed PM2.5 and O3 concentrations were 0.4-1.5 and 10.6-14.5 µg·m-3, respectively, suggesting that aviation emissions have become an increasingly important source of ambient air pollution. The contributions attributable to high-altitude emissions (climb/cruise/descent) were comparable to those at low altitudes (landing and takeoff). Aviation-attributed ambient PM2.5 and O3 exposures are estimated to have caused about 67,000 deaths in China in 2017, with populous coastal regions in Eastern China suffering the most due to the dense aviation activity. We recommend that industrial and policy stakeholders expedite an agenda of regulating air pollutants harmonized with decarbonization efforts for a more sustainable aviation future.

Association between sarcopenia-related traits and cardiovascular diseases: a bi-directional Mendelian randomization study.

Background: The two geriatric diseases, sarcopenia and cardiovascular disease (CVD), often coexist, yet the causal relationship is unclear. However, few studies focus on the effect of muscle mass on CVD. This comprehensive study is dedicated to unearthing the potential connection between sarcopenia-related traits and CVD at the genetic level. Method: A two-sample bi-directional Mendelian randomization (MR) study was conducted. In the first stage, we performed MR analysis regarding coronary heart disease (CHD), stroke, and myocardial infarction (MI) as exposure factors to reveal their effect on appendicular lean mass (ALM) and hand grip strength. In the second stage, we reverse the position of exposures and outcomes. The inverse variance weighted (IVW) method was used as the primary approach to reveal the potential causation between the exposure and outcome. Results: The results of the IVW method revealed a negative causal effect of ALM on CHD (OR = 0.848, 95% CI = 0.804 to 0.894, p = 8.200E-10), stroke (OR = 0.931, 95% CI = 0.890 to 0.975, p = 2.220E-03), and MI (OR = 0.810, 95% CI = 0.694 to 0.901, p = 1.266E-13). Additionally, the left-hand grip strength is a significant protective factor for CHD (OR = 0.737, 95% CI = 0.601 to 0.904, p = 3.353E-03) and MI (OR = 0.631, 95% CI = 0.515 to 0.765, p = 2.575E-06), but is not causally linked to the stroke (OR = 0.971, 95% CI =0.829 to 1.139, p = 0.720). Meanwhile, the same conclusion about the effect of right-hand grip strength on CHD (OR = 0.681, 95% CI = 0.558 to 0.832, p = 1.702E-05), MI (OR = 0.634, 95% CI = 0.518 to 0.776, p = 9.069E-06), and stroke (OR = 1.041, 95% CI = 0.896 to 1.209, p = 0.604) was obtained. However, no significant causal effect of CVD (CHD, stroke, MI) on sarcopenia-related traits (ALM, handgrip strength) was found. Conclusion: There is a unidirectional causal relationship between sarcopenia and CVD. The loss of muscle mass and strength has a significant causal role in promoting the occurrence and development of CVD, providing a reference for the prevention and treatment of comorbidities in older people.

Sonodynamic Therapy of NRP2 Monoclonal Antibody-Guided MOFs@COF Targeted Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis to Induce Autophagy-Dependent Ferroptosis.

The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron-based metal organic framework (Fe-MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer-specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non-targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule-associated protein 1A/1B-light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy-dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics.

Escin avoids hemorrhagic transformation in ischemic stroke by protecting BBB through the AMPK/Cav-1/MMP-9 pathway.

BACKGROUND: Hemorrhagic transformation (HT) seriously affects the clinical application of recombinant tissue plasminogen activator (rt-PA). The main strategy for combating HT is to keep the blood-brain barrier (BBB) stable. Escin is the active ingredient of Aesculus hippocastanum and a natural mixture of triterpene saponins, and may play a part in mitigation of HT. PURPOSE: This study sought to investigate the effect of Escin in improving rt-PA-induced HT, explore possible mechanisms, and provide new ideas for the treatment of clinical HT. STUDY DESIGN AND METHODS: In in vivo experiments, transient middle cerebral artery occlusion (tMCAO) was undertaken in 6-week-old and 12-month-old mice, and rt-PA was administered to induce HT injury. The inhibitory effect of Escin on HT and its protective effect on neurobehavior, the BBB, and cerebrovascular endothelial cells was determined. In in vitro experiments, bEnd.3 cells were injured by oxygen-glucose deprivation/reperfusion (OGD/R) and rt-PA. The protective effect of Escin was measured by the CCK8 assay, release of lactate dehydrogenase (LDH), and expression of tight junction (TJ) proteins. In mechanistic studies, the effect of Escin on the adenosine monophosphate-activated kinase / caveolin-1 / matrix metalloprotease-9 (AMPK/Cav-1/MMP-9) pathway was investigated by employing AMPK inhibitor and Cav-1 siRNA. RESULTS: In mice suffering from ischemia, rt-PA caused HT as well as damage to the BBB and cerebrovascular endothelial cells. Escin reduced the infarct volume, cerebral hemorrhage, improved neurobehavioral deficits, and maintained BBB integrity in rt-PA-treated tMCAO mice while attenuating bEnd.3 cells damage caused by rt-PA and OGD/R injury. Under physiological and pathological conditions, Escin increased the expression of p-AMPK and Cav-1, leading to decreased expression of MMP-9, which further attenuated damage to cerebrovascular endothelial cells, and these effects were verified with AMPK inhibitor and Cav-1 siRNA. CONCLUSION: We revealed important details of how Escin protects cerebrovascular endothelial cells from HT, these effects were associated with the AMPK/Cav-1/MMP-9 pathway. This study provides experimental foundation for the development of new drugs to mitigate rt-PA-induced HT and the discovery of new clinical application for Escin.

Adaptive response of flavonoids in Robinia pseudoacacia L. affected by the contamination of cadmium and elevated CO2 to arbuscular mycorrhizal symbiosis.

As a key component in non-enzyme resistance system, flavonoids play a crucial role in the plant growth and defenses, which are significantly affected by biotic and abiotic factors such as fungi, bacteria, viruses, heavy metals, and atmospheric CO2. Arbuscular mycorrhizal fungi (AMF) play an important role in enhancing plant tolerance to adverse environments, which can significantly affect the synthesis of flavonoids by forming mycorrhizal symbionts with plant roots. However, few studies explored the combined effects of AMF, elevated CO2, and heavy metals on flavonoids in plants. Here, we investigated the adaptive response of flavonoids accumulation in Robinia pseudoacacia L. seedlings affected by the contamination of cadmium (Cd) and elevated CO2 to arbuscular mycorrhizal symbiosis. The results showed that G. mosseae decreased (p < 0.05) Cd content in leaves by 62.2% under elevated CO2. Moreover, G. mosseae colonization led to significant decreases in robinin, quercetin, kaempferol and acacetin by 17.4%, 11.1%, 15.5% and 23.1% under elevated CO2 + Cd, respectively. Additionally, G. mosseae down-regulated (p < 0.05) expression levels of phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) genes under elevated CO2 + Cd, and CHS and uridine diphosphate flavonoid glucosyltransferase (UFGT) activities decreased (p < 0.05). Quercetin, kaempferol and acacetin showed positive (p < 0.05) correlation with PAL and CHS genes expression and PAL, CHS, and UFGT activities. Cadmium, C/N ratio, carotenoids, leaf biomass, total chlorophyll, P, and starch in leaves and G. mosseae colonization rate in roots influenced (p < 0.05) flavonoids content. Overall, G. mosseae reduced flavonoids synthesis by down-regulating gene expression levels and activities of key enzymes under elevated CO2 + Cd. The results improved our understanding of the regulation of AMF on non-enzymatic resistance of plants grown in heavy metal-contaminated soils under increasing atmospheric CO2 scenarios.

Plug & play origami modules with all-purpose deformation modes.

Three basic deformation modes of an object (bending, twisting, and contraction/extension) along with their various combinations and delicate controls lead to diverse locomotion. As a result, seeking mechanisms to achieve simple to complex deformation modes in a controllable manner is a focal point in related engineering fields. Here, a pneumatic-driven, origami-based deformation unit that offers all-purpose deformation modes, namely, three decoupled basic motion types and four combinations of these three basic types, with seven distinct motion modes in total through one origami module, was created and precisely controlled through various pressurization schemes. These all-purpose origami-based modules can be readily assembled as needed, even during operation, which enables plug-and-play characteristics. These origami modules with all-purpose deformation modes offer unprecedented opportunities for soft robots in performing complex tasks, which were successfully demonstrated in this work.

Design, synthesis, and biological evaluation of novel molecules as potent inhibitors of PLK1.

Polo-like kinase 1 (PLK1) is an attractive therapeutic target for the treatment of tumors, as it is an essential cell-cycle regulator frequently overexpressed in tumor tissues. PLK1 can promote tumor invasion and metastasis, and is often associated with poor prognosis in cancer patients. However, no PLK1 inhibitor has been granted marketing approval until now. Therefore, more potentially promising PLK1 inhibitors need to be investigated. In this study, a series of novel inhibitors targeting PLK1 was designed and optimized derived from a new scaffold. After synthesis and characterization, we obtained the structure-activity relationship and led to the discovery of the most promising compound 30e for PLK1. The antiproliferative activity against HCT116 cells (IC50 = 5 nM versus 45 nM for onvansertib) and the cellular permeability and efflux ratio were significantly improved (PappA→B = 2.03 versus 0.345 and efflux ratio = 1.65 versus 94.7 for 30e and onvansertib, respectively). Further in vivo studies indicated that 30e had favorable antitumor activity with 116.2% tumor growth inhibition (TGI) in comparison with TGI of 43.0% for onvansertib. Furthermore, 30e improved volume of tumor tissue distribution in mice as compared to onvansertib. This initial study on 30e holds promise for further development of an antitumor agent.

Biological evaluation and in silico studies of novel compounds as potent TAAR1 agonists that could be used in schizophrenia treatment.

Introduction: Schizophrenia is a serious mental illness that requires effective treatment with minimal adverse effects. As preclinical and clinical research progresses, trace amine-associated receptor 1 (TAAR1) is becoming a potential new target for the treatment of schizophrenia. Methods: We used molecular docking and molecular dynamics (MD) simulations to discover TAAR1 agonists. The agonistic or inhibitory effects of compounds on TAAR1, 5-HT1A, 5-HT2A, and dopamine D2-like receptors were determined. We used an MK801-induced schizophrenia-like behavior model to assess the potential antipsychotic effects of compounds. We also performed a catalepsy assay to detect the adverse effects. To evaluate the druggability of the compounds, we conducted evaluations of permeability and transporter substrates, liver microsomal stability in vitro, human ether-à-go-go-related gene (hERG), pharmacokinetics, and tissue distribution. Results: We discovered two TAAR1 agonists: compounds 50A and 50B. The latter had high TAAR1 agonistic activity but no agonistic effect on dopamine D2-like receptors and demonstrated superior inhibition of MK801-induced schizophrenia-like behavior in mice. Interestingly, 50B had favorable druggability and the ability to penetrate the blood-brain barrier (BBB) without causing extrapyramidal symptoms (EPS), such as catalepsy in mice. Conclusion: These results demonstrate the potential beneficial role of TAAR1 agonists in the treatment of schizophrenia. The discovery of a structurally novel TAAR1 agonist (50B) may provide valuable assistance in the development of new treatments for schizophrenia.

Study on Pharmacokinetics and Metabolic Profiles of Novel Potential PLK-1 Inhibitors by UHPLC-MS/MS Combined with UHPLC-Q-Orbitrap/HRMS.

PLK-1 (Polo-like kinase-1) plays an essential role in cytokinesis, and its aberrant expression is considered to be keenly associated with a wide range of cancers. It has been selected as an appealing target and small-molecule inhibitors have been developed and studied in clinical trials. Unfortunately, most have been declared as failures due to the poor therapeutic response and off-target toxicity. In the present study, a novel potent PLK-1 inhibitor, compound 7a, was designed and synthetized. 1H NMR, 13C NMR, 19F NMR and mass spectrum were comprehensively used for the compound characterization. The compound exhibited higher potency against PLK-1 kinase, HCT-116 and NCI-H2030 cell lines than the positive control. Molecular docking indicated that the binding mode that the ATP binding site of PLK-1 was occupied by the compound. Then, a UHPLC-MS/MS method was established and validated to explore the pharmacokinetic behavior of the drug candidate. The method had good selectivity, high sensitivity and wide linearity. The exposure increased linearly with the dose, but the oral bioavailability was not satisfactory enough. Then, the metabolism was studied using liver microsomes by UHPLC-Q-Orbitrap/HRMS. Our research first studied the pharmacokinetic metabolic characteristics of 7a and may serve as a novel lead compound for the development of PLK-1 inhibitors.

Classification and microsurgical treatment of foramen magnum meningioma.

BACKGROUND: To investigate the classification and microsurgical treatment of foramen magnum meningioma (FMM). METHODS: We retrospectively analyzed 76 patients with FMM and classified them into two classifications, classification ABS according to the relationship between the FMM and the brainstem and classification SIM according to the relationship between the FMM and the vertebral artery (VA). All patients underwent either the far lateral approach (54 cases) or the suboccipital midline approach (22 cases). RESULTS: Of the 76 cases, 47 cases were located ahead of the brainstem (A), 16 cases at the back of the brainstem (B), and 13 cases were located laterally to the brainstem (S). There were 15 cases located superior to the VA (S), 49 cases were inferior (I), and 12 cases were mixed type (M). Among 76 cases, 71 cases were resected with Simpson grade 2 (93.42%), 3 with Simpson grade 3 (3.95%), and 2 with Simpson grade 4 (2.63%). We summarized four anatomical triangles: triangles SOT, VOT, JVV, and TVV. The mean postoperative Karnofsky performance score was improved in all patients (p < 0.05). However, several complications occurred, including hoarseness and CSF leak. CONCLUSION: ABS and SIM classifications are objective indices for choosing the surgical approach and predicting the difficulty of FMMs, and it is of great importance to master the content, position relationship with the tumor, and variable anatomical structures in the four "triangles" for the success of the operation.

Role of kisspeptin in decidualization and unexplained recurrent spontaneous abortion via the ERK1/2 signalling pathway.

INTRODUCTION: This study aimed to study the expression and function of kisspeptin during human uterine decidualization in recurrent spontaneous abortion (RSA) and the underlying mechanism. METHODS: All patients were recruited from the Clinical Reproductive Center of the Second Affiliated Hospital of Soochow University. Mice models of RSA (CBA/J × DBA/2) and normal pregnancy (CBA/J × BALB/c) were established, respectively. Kisspeptin expression in the serum and decidual tissues of women with RSA were detected. The function of kisspeptin during decidualization in human endometrial stromal cells (HESCs) was assessed by enhancing and silencing kisspeptin expression. CBA/J × DBA/2 pregnant mice were injected with kisspeptin polypeptide, kisspeptin receptor blocker, and expression of decidualization markers was observed. The regulation of ERK1/2 signalling pathway were verified. RESULTS: Serum kisspeptin levels were significantly lower in patients with RSA than in normal pregnant individuals, as was the expression of kisspeptin, p-ERK, and decidualization indicators in the decidua. Additionally, kisspeptin inhibition downregulated the expression of decidualization markers in HESCs. In mice with RSA, kisspeptin was significantly downregulated, and p-ERK expression at the maternal-foetal interface was significantly decreased. Moreover, exogenous kisspeptin supplementation improved the levels of IGFBP-1 and dPRL, upregulated p-ERK expression, and reduced the abortion rate. DISCUSSION: Kisspeptin is involved in promoting uterine decidualization via the ERK1/2 signalling pathway.

Vehicular Ammonia Emissions Significantly Contribute to Urban PM2.5 Pollution in Two Chinese Megacities.

Ammonia (NH3) plays a vital role in the formation of fine particulate matter (PM2.5). Prior studies have primarily focused on the control of agricultural NH3 emissions, the dominant source of anthropogenic NH3 emissions. The air quality impact from vehicular NH3 emissions, which could be particularly important in urban areas, has not been adequately evaluated. We developed high-resolution vehicular NH3 emission inventories for Beijing and Shanghai based on detailed link-level traffic profiles and conducted atmospheric simulations of ambient PM2.5 concentrations contributed by vehicular NH3 emissions. We found that vehicular NH3 emissions shared high proportions among total anthropogenic NH3 emissions in the urban areas of Beijing (86%) and Shanghai (45%), where vehicular NH3 was primarily emitted by gasoline vehicles. Local vehicular NH3 emissions could be responsible for approximately 3% of urban PM2.5 concentrations during wintertime, and the contributions could be much higher during polluted periods (∼3 µg m-3). We also showed that controlling vehicular NH3 emissions will be effective and feasible to alleviate urban PM2.5 pollution for megacities in the near future.

Effect of Glomus mosseae, cadmium, and elevated air temperature on main flavonoids and phenolic acids contents in alfalfa.

Global warming and heavy metal-contaminated soils co-occur in natural ecosystems. Flavonoids and phenolic acids in plants have significant antioxidant activity and free radical scavenging ability, which can quickly increase under adverse environments. Arbuscular mycorrhizal fungi (AMF) colonization can affect the synthesis of flavonoids and phenolic acids in host plants. This study focused on the main effect of Glomus mosseae, cadmium (Cd, 8 mg kg-1 dry soils), and elevated temperature (ET, + 3 °C) on main flavonoids and phenolic acids in 120-d Medicago sativa L. (alfalfa). Elevated temperature decreased G. mosseae colonization ratio by 49.5% under Cd exposure. Except for p-hydroxybenzoic acid, flavonoids and phenolic acids content in shoots increased (p < 0.05) under G. mosseae + Cd relative to Cd only. G. mosseae and Cd showed significant effects on rutin, quercetin, apigenin, liquiritigenin, gallic acid, p-hydroxybenzoic acid, p-coumaric acid, and ferulic acid, and G. mosseae colonization led to increases in these compounds by 41.7%, 35.4%, 32.2%, 267.8%, 84.7%, 33.5%, 102.8%, and 89.4%, respectively, under ET + Cd. Carbon, N, and Cd in alfalfa and G. mosseae colonization rate were significant factors on flavonoids and phenolic acids accumulation. Additionally, P content in shoots significantly influenced flavonoids content. G. mosseae inoculation significantly stimulated the synthesis of main flavonoids and phenolic acids in alfalfa shoots under ET + Cd, which was helpful to understand the regulation of AMF on non-enzyme antioxidant system of plants grown in heavy metal-contaminated soils under global change scenarios.

Heavy-metal resistant bio-hybrid with biogenic ferrous sulfide nanoparticles: pH-regulated self-assembly and wastewater treatment application.

Self-assembled bio-hybrids with biogenic ferrous sulfide nanoparticles (bio-FeS) on the cell surface are attractive for reduction of toxic heavy metals due to higher activity than bare bacteria, but they still suffer from slow synthesis and regeneration of bio-FeS and bacterial activity decay for removal of high-concentration heavy metals. A further optimization of the bio-FeS synthesis process and properties is of vital importance to address this challenge. Herein, we present a simple pH-regulation strategy to enhance bio-FeS synthesis and elucidated the underlying regulatory mechanisms. Slightly raising the pH from 7.4 to 8.3 led to 1.5-fold higher sulfide generation rate due to upregulated expression of thiosulfate reduction-related genes, and triggered the formation of fine-sized bio-FeS (29.4 ± 6.1 nm). The resulting bio-hybrid exhibited significantly improved extracellular reduction activity and was successfully used for treatment of high-concentration chromium -containing wastewater (Cr(VI), 80 mg/L) at satisfactory efficiency and stability. Its feasibility for bio-augmented treatment of real Cr(VI)-rich electroplating wastewater was also demonstrated, showing no obvious activity decline during 7-day operation. Overall, our work provides new insights into the environmental-responses of bio-hybrid self-assembly process, and may have important implications for optimized application of bio-hybrid for wastewater treatment and environmental remediation.

The etiology of poststroke-depression: a hypothesis involving HPA axis.

Approximately, one in three ischemic stroke survivors suffered from depression, namely, post-stroke depression (PSD). PSD affects functional rehabilitation and may lead to poor quality of life of patients. There are numerous explanations about the etiologies of PSD. Here, we speculated that PSD are likely to be the result of specific changes in brain pathology. We hypothesized that the stroke-induced hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis plays an important role in PSD. Stroke initiates a complex sequence of events in neuroendocrine system including HPA axis. The HPA axis is involved in the pathophysiology of depression, especially, the overactivity of the HPA axis occurs in major depressive disorder. This review summarizes the possible etiologies of PSD, focusing on the stroke-induced activation of HPA axis, mainly including the stress followed by severe brain damage and the proinflammatory cytokines release. The role of hyperactive of HPA axis in PSD was discussed in detail, which includes the role of high level corticotropin-releasing hormone in PSD, the effects of glucocorticoids on the alterations in specific brain structures, the expression of enzymes, excitotoxicity, the change in intestinal permeability, and the activation of microglia. The relationship between neuroendocrine regulation and inflammation was also described. Finally, the therapy of PSD by regulating HPA axis, neuroendocrine, and immunity was discussed briefly. Nevertheless, the change of HPA axis and the occurring of PSD maybe interact and promote on each other, and future investigations should explore this hypothesis in more depth.

Metal-Organic Framework Composite Photothermal Membrane for Removal of High-Concentration Volatile Organic Compounds from Water via Molecular Sieving.

Water-soluble volatile organic compounds (VOCs) are among the most difficult-to-treat species during wastewater treatment. The current purification and removal of high-concentration VOCs still rely on the energy-consuming distillation and high-pressure driven reverse osmosis technology. There is an urgent need for an advanced technology that can effectively remove high-concentration VOCs from water. Here, we report a metal-organic framework (MOF)/polyaniline (PANI) nanofiber array composite photothermal membrane for removal of high-concentration VOCs from water via molecular sieving during a solar-driven evaporation process. The modified zeolitic imidazole framework-8 (ZIF-8) layer grown on a PANI nanofiber array acts as a molecular sieving layer to evaporate water but intercept VOCs. The composite membrane exhibits high VOCs rejection and a high-water evaporation rate for water containing different concentrations of VOCs. When treating water containing VOCs with a concentration of up to 400 mg L-1, the VOCs rejection rate is up to 99% and the water evaporation rate is 1.0 kg m-2 h-1 under 1 sun irradiation (1 kW m-2). Our work effectively combines the molecular sieve effect with a solar-driven evaporation process, which provides an effective strategy for the treatment of water containing VOCs.

The prognostic role of M2 tumor-associated macrophages in non-small-cell lung cancer.

Lung cancer is a high-risk tumor and is a main cause of death worldwide. The tumor aggressiveness and degree of malignancy depend not only on the tumor itself, but also on the microenvironment. The inflammatory microenvironment is one of the key factors in promoting the progression of lung cancer. It has been found that macrophages are the most abundant immune cells in the tumor microenvironment, with strong plasticity and heterogeneity. Tumor-Associated Macrophages (TAMs) are important components of the tumor immune microenvironment. TAMs are thought to be polarized into two main phenotypes: inflammatory or classically activated (M1) and antiinflammatory or alternatively activated (M2) macrophages. Their phenotype and function change according to environment and the appearance of tumor cells. M2 macrophages have been reported to be protumorigenic, because they can promote the formation of blood vessels in the tumor microenvironment, helping tumor cells escape the body's immune defense and promote their growth, by releasing a variety of cytokines, including chemokines, inflammatory factors and growth factor. However, the prognostic impact of TAMs and their phenotypes in non-small-cell lung cancer (NSCLC) remains to be fully elucidated. Some reports of the association between the characteristics of macrophages in lung tumor and patients' survival outcomes show contradicting results. In order to explore the prognostic role of TAMs in NSCLS, the association between the phenotype, density and distribution of macrophages and the prognosis of human NSCLC, as well as the potential mechanisms of M2 macrophages leading to poor prognosis in NSCLC, are reviewed in this study.