Self-assembled dendrimer polyamide nanofilms with enhanced effective pore area for ion separation.

Membrane technology using well-defined pore structure can achieve high ion purity and recovery. However, fine-tuning the inner pore structure of the separation nanofilm to be uniform and enhance the effective pore area is still challenging. Here, we report dendrimers with different peripheral groups that preferentially self-assemble in aqueous-phase amine solution to facilitate the formation of polyamide nanofilms with a well-defined effective pore range and uniform pore structure. The high permeabilities are maintained by forming asymmetric hollow nanostripe nanofilms, and their well-designed ion effective separation pore ranges show an enhancement, rationalized by molecular simulation. The self-assembled dendrimer polyamide membrane provides Cl-/SO42- selectivity more than 17 times that of its pristine polyamide counterparts, increasing from 167.9 to 2883.0. Furthermore, the designed membranes achieve higher Li purity and Li recovery compared to current state-of-the-art membranes. Such an approach provides a scalable strategy to fine-tune subnanometre structures in ion separation nanofilms.

The impact of environmental regulation on renewable energy development in China from the perspective of spatial effects.

From a spatial perspective, this paper constructs a spatial Durbin model based on the adjacent weight matrix to analyze the impact of environmental regulation on the development of renewable energy in 30 provinces (autonomous regions and municipalities directly under the Central Government) in China from 2007 to 2020. The results show that (1) both environmental regulation and renewable energy development have positive spatial autocorrelation and form relatively similar spatial agglomeration areas, specifically showing the characteristics of "high-high" agglomeration in resource-rich areas and "low-low" agglomeration in resource-scarce areas. (2) Environmental regulation significantly promotes the development of local renewable energy and has a significant spatial spillover effect on the development of renewable energy in neighboring provinces. (3) The moderating effect results show that renewable energy installed capacity and electricity demand play an inverse moderating role between environmental regulation and renewable energy development. (4) From the perspective of different regions, the impact of environmental regulation on the development of renewable energy is heterogeneous. Based on the research conclusions, this paper finally provides corresponding policy suggestions from three aspects: regional cooperation, technical support, and differentiation.

Changes in Mental Health and EEG Biomarkers of Undergraduates Under Different Patterns of Mindfulness.

The effects of short-term mindfulness are associated with the different patterns (autonomic, audio guided, or experienced and certified mindfulness instructor guided mindfulness). However, robust evidence for reported the impacts of different patterns of mindfulness on mental health and EEG biomarkers of undergraduates is currently lacking. Therefore, we aimed to test the hypotheses that mindfulness training for undergraduates would improve mental health, and increase alpha power over frontal region and theta power over midline region at the single electrode level. We also describe the distinction among frequency bands patterns in different sites of frontal and midline regions. 70 participants were enrolled and assigned to either 5-day mindfulness or a waiting list group. Subjective questionnaires measured mental health and other psychological indicators, and brain activity was recorded during various EEG tasks before and after the intervention. The 5-day mindfulness training improved trait mindfulness, especially observing (p = 0.001, d = 0.96) and nonreactivity (p = 0.03, d = 0.56), sleep quality (p = 0.001, d = 0.91), and social support (p = 0.001, d = 0.95) while not in affect. Meanwhile, the expected increase in the alpha power of frontal sites (p < 0.017, d > 0.84) at the single electrode level was confirmed by the current data rather than the theta. Interestingly, the alteration of low-beta power over the single electrode of the midline (p < 0.05, d > 0.71) was difference between groups. Short-term mindfulness improves practitioners' mental health, and the potentially electrophysiological biomarkers of mindfulness on neuron oscillations were alpha activity over frontal sites and low-beta activity over midline sites.

Nomogram predicting surgical risk of laparoscopic left-sided hepatectomy for hepatolithiasis.

OBJECTIVE: To explore the surgical risk factors of laparoscopic left-sided hepatectomy for hepatolithiasis and establish and validate a nomogram to estimate the corresponding surgical risks. METHODS: Patients with hepatolithiasis who underwent laparoscopic left-sided hepatectomy were retrospectively enrolled. Demographic data, clinicopathological parameters, and surgical factors were collected. Three hundred fifty-three patients were enrolled and randomly divided into training set (n=267) and validation set (n=86) by 3:1. Conversion to laparotomy was used as a surrogate index to evaluate the surgical risk. Univariate analysis was used to screen potential surgical risk factors, and multivariate analysis using logistic regression model was used to screen independent surgical risk factors. Nomogram predicting the surgical risks was established based on the independent risk factors. Discrimination, calibration, decision curve, and clinical impact analyses were used to evaluate the performance of the nomogram on the statistical and clinical aspects both in the training and validation sets. RESULTS: Five independent surgical risk factors were identified in the training set, including recurrent abdominal pain, bile duct stricture, ASA classification ≥2, extent of liver resection, and biliary tract T tube drainage. No collinearity was found among these five factors, and a nomogram was established. Performance analyses of the nomogram showed good discrimination (AUC=0.850 and 0.817) and calibration (Hosmer-Lemeshow test, p=0.530 and 0.930) capabilities both in the training and validation sets. Decision curve and clinical impact analyses also showed that the prediction performance was clinically valuable. CONCLUSIONS: A nomogram was established and validated to be effective in evaluating and predicting the surgical risk of patients undergoing laparoscopic left-sided hepatectomies for hepatolithiasis.

Exploring Applicability of Different Ecological Protection Measures for Soil and Water Loss Control of Highway Slope in the Permafrost Area: A Case Study of Qinghai-Tibet Highway in China.

A variety of slope water and soil conservation measures have been taken along the Qinghai-Tibet Highway, but the systematic comparison of their erosion control ability needs to be strengthened, especially in the permafrost area. To explore the applicability of different measures to control runoff and sediment yield, field scouring experiments were conducted for different ecologically protected slopes, including turfing (strip, block, full), slope covering (gravel, coconut fiber blanket), and comprehensive measures (three-dimensional net seeding). Compared with the bare slope, the bulk density of the plots with the ecological protection measure decreased, the moisture-holding capacity and the organic matter increased correspondingly, and the average runoff velocity also decreased. The soil loss and runoff had a similar trend of different ecological protection measures. The relationship between the cumulative runoff and sediment yield of different measures exhibited a power function, with the increase of scouring flow and the runoff reduction benefit and sediment reduction benefit in different ecological protection-measured plots showing a decreasing trend. The average runoff reduction benefit decreased from 37.06% to 6.34%, and the average sediment reduction benefit decreased from 43.04% to 10.86%. The comprehensive protection measures had the greatest protection efficiency, followed by turfing, while the cover measure had limited improvement. Soil characteristics, vegetation coverage, and the scouring inflow rate are key factors that influence protection efficiency. The results suggest that comprehensive measures and turfing be taken rather than cover measures or bare slopes. This work provides an experimental reference for ecological protection methods for highway slopes in the permafrost area.

Systematic Adaptation of Bacillus licheniformis to 2-Phenylethanol Stress.

The compound 2-phenylethanol (2-PE) is a bulk flavor and fragrance with a rose-like aroma that can be produced by microbial cell factories, but its cellular toxicity inhibits cellular growth and limits strain performance. Specifically, the microbe Bacillus licheniformis has shown a strong tolerance to 2-PE. Understanding these tolerance mechanisms is crucial for achieving the hyperproduction of 2-PE. In this report, the mechanisms of B. licheniformis DW2 resistance to 2-PE were studied by multi-omics technology coupled with physiological and molecular biological approaches. 2-PE induced reactive oxygen species formation and affected nucleic acid, ribosome, and cell wall synthesis. To manage 2-PE stress, the antioxidant and global stress response systems were activated; the repair system of proteins and homeostasis of the ion and osmotic were initiated. Furthermore, the tricarboxylic acid cycle and NADPH synthesis pathways were upregulated; correspondingly, scanning electron microscopy revealed that cell morphology was changed. These results provide deeper insights into the adaptive mechanisms of B. licheniformis to 2-PE and highlight the potential targets for genetic manipulation to enhance 2-PE resistance. IMPORTANCE The ability to tolerate organic solvents is essential for bacteria producing these chemicals with high titer, yield, and productivity. As exemplified by 2-PE, bioproduction of 2-PE represents a promising alternative to chemical synthesis and plant extraction approaches, but its toxicity hinders successful large-scale microbial production. Here, a multi-omics approach is employed to systematically study the mechanisms of B. licheniformis DW2 resistance to 2-PE. As a 2-PE-tolerant strain, B. licheniformis displays multifactorial mechanisms of 2-PE tolerance, including activating global stress response and repair systems, increasing NADPH supply, changing cell morphology and membrane composition, and remodeling metabolic pathways. The current work yields novel insights into the mechanisms of B. licheniformis resistance to 2-PE. This knowledge can also be used as a clue for improving bacterial performances to achieve industrial-scale production of 2-PE and potentially applied to the production of other relevant organic solvents, such as tyrosol and hydroxytyrosol.

Non-canonical binding of the Chaetomium thermophilum PolD4 N-terminal PIP motif to PCNA involves Q-pocket and compact 2-fork plug interactions but no 310 helix.

DNA polymerase δ (Pol δ) is a key enzyme for the maintenance of genome integrity in eukaryotic cells, acting in concert with the sliding clamp processivity factor PCNA (proliferating cell nuclear antigen). Three of the four subunits of human Pol δ interact directly with the PCNA homotrimer via a short, conserved protein sequence known as a PCNA interacting protein (PIP) motif. Here, we describe the identification of a PIP motif located towards the N terminus of the PolD4 subunit of Pol δ (equivalent to human p12) from the thermophilic filamentous fungus Chaetomium thermophilum and present the X-ray crystal structure of the corresponding peptide bound to PCNA at 2.45 Å. Like human p12, the fungal PolD4 PIP motif displays non-canonical binding to PCNA. However, the structures of the human p12 and fungal PolD4 PIP motif peptides are quite distinct, with the fungal PolD4 PIP motif lacking the 310 helical segment that characterises most previously identified PIP motifs. Instead, the fungal PolD4 PIP motif binds PCNA via conserved glutamine that inserts into the Q-pocket on the surface of PCNA and with conserved leucine and phenylalanine sidechains forming a compact 2-fork plug that inserts into the hydrophobic pocket on PCNA. Despite the unusual binding mode of the fungal PolD4, isothermal calorimetry (ITC) measurements show that its affinity for PCNA is similar to that of its human orthologue. These observations add to a growing body of information on how diverse proteins interact with PCNA and highlight how binding modes can vary significantly between orthologous PCNA partner proteins.

Research on the Formation Mechanism of Health Insurance Fraud in China: From the Perspective of the Tripartite Evolutionary Game.

The problem of fraud in China's health insurance has existed for a long time and is becoming more serious, which needs to be solved urgently. This article constructs a tripartite evolutionary game model to study the formation mechanism of the Health Insurance fraud, game participants including medical administrative organization (MAO, a government department responsible for health insurance supervision), medical institutions (MI, such as hospitals), and insured individuals (II, who participating in medical and healthcare insurance). By analyzing the equilibrium of the tripartite evolutionary game, this paper makes an in-depth study on the formation and resolution of health insurance fraud. The results show that: (1) How to prevent the fraud behavior of the medical institutions is the difficulty and core of the problem. It is necessary to achieve effective supervision of the MAO, improve the internal management of the MI and give play to the supervisory role of the II. (2) The regulatory behavior of the MAO needs to focus on protecting the interests of the II, not only to encourage them to actively play the role of supervision and reporting but also to prevent their collusion with MI. (3) On the one hand, the MAO needs to strengthen supervision and increase the punishment for fraud. On the other hand, they also need to take incentive measures to guide all subjects to form a sound internal management mechanism.

Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer.

As one of the most common forms of solid tumours, gastric carcinoma has been revealed as the third leading cause of death worldwide. The symptom of gastric cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, gastric cancer is already in the advanced stage once detected in patients, which has a poor prognosis due to ineffective therapies and multiple resistance. Recent advance in understanding the microenvironment of cancer has significantly promoted the development of immunotherapy for advanced gastric cancer. Immunotherapy can induce immune responses in gastric cancer patients thus leads to the destruction of cancer cells. In comparison of traditional therapy, immunotherapy has demonstrated robust efficacy and tolerable toxicity. Therefore, this novel strategy for treatment of advanced gastric cancer has gain increasingly popularity. In this review, we summarize recent progress of immunotherapy in advanced gastric cancer, such as immune check point inhibitors, adoptive cell therapy, VEGF inhibitors, cancer vaccines and CAR-T cell therapy. We highlight immunotherapies involved in clinical applications and discuss the existing challenges of current immunotherapies and promising strategies to overcome these limitations.

Potentialities and Challenges of mRNA Vaccine in Cancer Immunotherapy.

Immunotherapy has become the breakthrough strategies for treatment of cancer in recent years. The application of messenger RNA in cancer immunotherapy is gaining tremendous popularity as mRNA can function as an effective vector for the delivery of therapeutic antibodies on immune targets. The high efficacy, decreased toxicity, rapid manufacturing and safe administration of mRNA vaccines have great advantages over conventional vaccines. The unprecedent success of mRNA vaccines against infection has proved its effectiveness. However, the instability and inefficient delivery of mRNA has cast a shadow on the wide application of this approach. In the past decades, modifications on mRNA structure and delivery methods have been made to solve these questions. This review summarizes recent advancements of mRNA vaccines in cancer immunotherapy and the existing challenges for its clinical application, providing insights on the future optimization of mRNA vaccines for the successful treatment of cancer.

Maternal factor NELFA drives a 2C-like state in mouse embryonic stem cells.

Mouse embryonic stem cells (ESCs) sporadically transit into an early embryonic-like state characterized by the expression of 2-cell (2C) stage-restricted transcripts. Here, we identify a maternal factor-negative elongation factor A (NELFA)-whose heterogeneous expression in mouse ESCs is coupled to 2C gene upregulation and expanded developmental potential in vivo. We show that NELFA partners with Top2a in an interaction specific to the 2C-like state, and that it drives the expression of Dux-a key 2C regulator. Accordingly, loss of NELFA and/or Top2a suppressed Dux activation. Further characterization of 2C-like cells uncovered reduced glycolytic activity; remarkably, mere chemical suppression of glycolysis was sufficient to promote a 2C-like fate, obviating the need for genetic manipulation. Global chromatin state analysis on NELFA-induced cells revealed decommissioning of ESC-specific enhancers, suggesting ESC-state impediments to 2C reversion. Our study positions NELFA as one of the earliest drivers of the 2C-like state and illuminates factors and processes that govern this transition.

GRP78 activates the Wnt/HOXB9 pathway to promote invasion and metastasis of hepatocellular carcinoma by chaperoning LRP6.

Recent studies have shown that the expression levels of glucose-regulated protein 78 (GRP78) and homeobox B9 (HOXB9) are both upregulated in hepatocellular carcinoma (HCC) and are closely related to HCC invasion and metastasis. However, whether there is a regulatory relationship between GRP78 and HOXB9 is unclear. In this study, we examined the expression of GRP78 and HOXB9 in HCC tissues and adjacent nontumor tissues. Correlation analysis indicated that GRP78 and HOXB9 expression were positively correlated. High levels of GRP78 and HOXB9 expression are closely related to worse clinicopathological features. Knockdown of GRP78 in HCC cells decreased the mRNA and protein expression of HOXB9, but increase HOXB9 expression reversed the decrease in invasion and metastasis induced by knocking down GRP78. Further experiments showed that GRP78 regulates HOXB9 through the Wnt signaling pathway by chaperoning low-density lipoprotein receptor-related protein 6 (LRP6). Importantly, we found that GPR78 promoted maturation of LRP6, while knockdown of GRP78 led to LRP6 misfolding and endoplasmic reticulum-associated degradation (ERAD). Consequently, the levels of mature LRP6 were reduced, and Wnt/HOXB9 signaling was inhibited. Our data suggest that the GRP78-LRP6-HOXB9 axis regulates the invasion and metastasis of HCC and may represent a potential therapeutic target for the treatment of HCC.

Bi-functional nitrogen-doped carbon protective layer on three-dimensional RGO/SnO2 composites with enhanced electron transport and structural stability for high-performance lithium-ion batteries.

Three-dimensional reduced graphene oxide@SnO2@nitrogen-doped carbon (3DG@SnO2@N-C) composites are designed as high efficiency anode materials for lithium-ion batteries. The SnO2 particle size, surface area and pore size distribution of the 3DG@SnO2@N-C could be simply controlled by altering the GO dosages. The optimized 3DG@SnO2@N-C electrode demonstrates a reversible capacity of 1349.5 mAh g-1 after 100 cycles at the current density of 100 mA g-1. Based on the structural and electrochemical dynamic tests, the bi-functional N-doped carbon coating layer could serve as both conductive channel for electron transport and as buffer layer to alleviate the volume change of embedded SnO2 NPs. In addition, the cross-linked conducting 3DG with porous structure attributes to the reduced electron transport and Li ion diffusion resistances, which finally leads to the enhanced cycling stability and rate performances.

MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells.

Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. T(4;14) MM overexpresses multiple myeloma SET domain-containing protein (MMSET). MMSET has three major isoforms: the full-length form MMSET II and the short isoforms REIIBP and MMSET I. Here we show that the short isoform MMSET I is an oncoprotein that promoted cell survival and tumorigenesis in vitro and in vivo. Gene expression array analysis indicated that MMSET I increased glyoxalase I (GLO1) expression. Chromatin immunoprecipitation (ChIP) coupled with qPCR indicated that MMSET I bound upstream of the GLO1 transcription start site. Ectopic overexpression of MMSET I or its mutants showed MMSET I depended on its C terminus to regulate GLO1 expression. GLO1 knockdown (KD) induced apoptosis and reduced colony formation. MMSET I or GLO1 KD reduced the levels of anti-apoptosis factors such as MCL1 and BCL2. Ectopic overexpression of GLO1 resulted in the significant rescue of KMS11 cells from MMSET I KD-induced apoptosis and glycolysis inhibition. This suggested that GLO1 may be of functional importance target downstream of MMSET I. Cumulatively, our study suggests that MMSET I is an oncoprotein and potential therapeutic target for t(4;14) MM.

Enhanced performance of a graphene/GaAs self-driven near-infrared photodetector with upconversion nanoparticles.

Near-infrared photodetectors (NIRPDs) have attracted great attention because of their wide range of applications in many fields. Herein, a novel self-driven NIRPD at the wavelength of 980 nm is reported based on the graphene/GaAs heterostructure. Extraordinarily, its sensitivity to light illumination (980 nm) is far beyond the absorption limitation of GaAs (874 nm). This means that the photocurrent originates from the separation of photo-induced carriers in graphene, which is caused by the vertically built-in electric field formed through the high quality van der Waals contact between graphene and GaAs. Moreover, after introducing NaYF4:Yb3+/Er3+ upconversion nanoparticles (UCNPs) onto the graphene/GaAs heterojunction, the responsivity increases to be as superior as 5.97 mA W-1 and the corresponding detectivity is 1.1 × 1011 cm Hz0.5 W-1 under self-driven conditions. This dramatic improvement is mainly ascribed to the radiative energy transfer from UCNPs to the graphene/GaAs heterostructure. The high-quality and self-driven UCNPs/graphene/GaAs heterostructure NIRPD holds significant potential for practical application in low-consumption and large-scale optoelectronic devices.

Selective anticancer activity of the novel steroidal dihydropyridine spirooxindoles against human esophageal EC109 cells.

A series of small-molecule compounds built on steroidal dihydropyridine spirooxindoles has been reported previously. In this study, the compound 5l showed strong anti-cancer activity, especially in the esophageal cancer. Three esophageal squamous cell lines and paclitaxel-resistant cell line were investigated. The results demonstrated that compound 5l was most efficient in the EC109 cells, induced cell apoptosis through elevation of cellular ROS levels, caused G2/M phase arrest and mitochondrial dysfunction. Further study confirmed that the mechanism of 5l in esophageal cancer treatment was related to the Bcl-2 family and caspase receptor-mediated apoptotic pathway.

Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line.

Paclitaxel (PTX) is one of the most effective drugs used in the treatment of esophageal cancer, however, paclitaxel resistance represents a key limitation during the treatment process. In this study, we investigated the changes of Bcl-2 family members in the moderate paclitaxel-resistance of esophageal carcinoma EC109/PTX cells both in vitro and in vivo. Moreover, we evaluated the reversal effect using siRNAs and the recombinant inhibitor TW37 targeting Bcl-2, Bcl-XL and Mcl-1. Our findings show that downregulation of Bcl-2, Bcl-XL and Mcl-1 can significantly promote EC109/PTX cell apoptosis and reduce the EC109/PTX cell resistance index (RI). Furthermore, TW37 in combination with a P-gp inhibitor can synergistically reverse the paclitaxel resistance in EC109/PTX cells. These results suggest that targeting of the Bcl-2 family and P-gp is capable of reversing the resistance in EC109/PTX cells and the two-inhibitor combination may be a novel treatment strategy for resistant esophageal cancer.

Highly efficient graphene-on-gap modulator by employing the hybrid plasmonic effect.

We propose a highly efficient graphene-on-gap modulator (GOGM) by employing the hybrid plasmonic effect, whose modulation efficiency (up to 1.23 dB/µm after optimization) is ∼12-fold larger than that of the present graphene-on-silicon modulator (∼0.1 dB/µm). The proposed modulator has the advantage of a short modulation length of ∼3.6 µm, a relatively low insertion loss of ∼0.32 dB, and a larger modulation bandwidth of ∼0.48 THz. The physical insight is investigated, showing that both the slow light effect and the overlap between graphene and the mode field contribute. Moreover, an efficient taper coupler has been designed to convert the quasi-transverse electric mode of conventional silicon waveguide to the hybrid plasmonic mode of GOGM, with a high coupling efficiency of 91%. This Letter may promote the design of high-performance on-chip electro-optical modulators.

Bone morphogenetic protein 4 is overexpressed in and promotes migration and invasion of drug-resistant cancer cells.

Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-ß superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc). In these drug-resistant cell lines, we found the cell motility was enhanced and BMP4 was up-regulated relative to their respective parental cell lines. Consistent with in vitro assays, migration potential and BMP4 expression were increased in EC109/Taxol nude mice. Furthermore, to address whether BMP4 was required to enhance the metastatic in EC109/Taxol cells, the pharmacological inhibitor of BMP signaling dorsomorphin was used; meanwhile, we found that the migration and invasion abilities were inhibited. Moreover, the canonical Smad signaling pathway was investigated. Overall, our studies demonstrated that BMP4 participates in the regulation of invasion and migration by EC109/Taxol cells, and inhibition of BMP4 may be a novel strategy to interfere with metastasis in cancer therapy.

Jesridonin in combination with paclitaxel demonstrates synergistic anti-tumor activity in human esophageal carcinoma cells.

The novel compound jesridonin, has extensive anti-tumor activity. In this study, we aim to investigate the cytotoxic effects of jesridonin in combination with paclitaxel. Our results showed that jesridonin in combination with paclitaxel had synergistic cytotoxic effects on human esophageal carcinoma both in vitro and in vivo. Hoechst 33258 staining and the Annexin-V FITC assay demonstrated that paclitaxel synergized with jesridonin in a stronger induction of apoptosis than treatment with paclitaxel or jesridonin alone. Western blotting results revealed that the synergistic apoptosis-induction effects of paclitaxel and jesridonin were mediated by the mitochondrial pathway. This may provide a novel strategy to overcome drug resistance for esophageal cancer therapy.