ComplexQA: a deep graph learning approach for protein complex structure assessment.

MOTIVATION: In recent years, the end-to-end deep learning method for single-chain protein structure prediction has achieved high accuracy. For example, the state-of-the-art method AlphaFold, developed by Google, has largely increased the accuracy of protein structure predictions to near experimental accuracy in some of the cases. At the same time, there are few methods that can evaluate the quality of protein complexes at the residue level. In particular, evaluating the quality of residues at the interface of protein complexes can lead to a wide range of applications, such as protein function analysis and drug design. In this paper, we introduce a new deep graph neural network-based method ComplexQA, to evaluate the local quality of interfaces for protein complexes by utilizing the residue-level structural information in 3D space and the sequence-level constraints. RESULTS: We benchmark our method to other state-of-the-art quality assessment approaches on the HAF2 and DBM55-AF2 datasets (high-quality structural models predicted by AlphaFold-Multimer), and the BM5 docking dataset. The experimental results show that our proposed method achieves better or similar performance compared with other state-of-the-art methods, especially on difficult targets which only contain a few acceptable models. Our method is able to suggest a score for each interfac e residue, which demonstrates a powerful assessment tool for the ever-increasing number of protein complexes. AVAILABILITY: https://github.com/Cao-Labs/ComplexQA.git. Contact: caora@plu.edu.

Thin-Film Composite Membranes Interlayered with Amphiphilic MoS2 Nanosheets via Controllable Interfacial Polymerization for Enhanced Desalination Performance.

Polyamide (PA)-based nanofiltration (NF) membranes have demonstrated extensive applications for a sustainable water-energy-environment nexus. A rational control of interfacial polymerization (IP) is highly efficacious to enhance NF separation performance yet remains a technical challenge. Herein, we proposed a regulation strategy of constructing amphiphilic molybdenum disulfide/cetyltrimethylammonium bromide interlayer atop the Kevlar hydrogel substrate. The amphiphilic nanosheet interlayered NF membrane exhibited a crumpled PA surface with an elevated cross-linking degree of 76.9%, leading to an excellent water permeance (16.8 L m-2 h-1 bar-1) and an impressive Na2SO4 rejection (99.1%). Meanwhile, the selectivity coefficient of Na2SO4/NaCl of the optimized TFC membrane reached 91, surpassing those of the recently reported NF membranes. Moreover, the optimized membrane exhibited a desirable rejection of over 90% against Mn2+ and Cu2+ in actual textile wastewater. Importantly, the underlying NF membrane formation mechanism was elucidated via both experiments and molecular simulations. The synchronous control of mass and heat transfer of IP process offers a new methodology for the state-of-the-art membrane fabrication, which opens more avenues in softening of brackish water and purification of industrial wastewater containing heavy metal ions.

Rational Design of MXene Hollow Fiber Membranes for Gas Separations.

One scalable and facile dip-coating approach was utilized to construct a thin CO2-selection layer of Pebax/PEGDA-MXene on a hollow fiber PVDF substrate. An interlayer spacing of 3.59 Å was rationally designed and precisely controlled for the MXene stacks in the coated layer, allowing efficient separation of the CO2 (3.3 Å) from N2 (3.6 Å) and CH4 (3.8 Å). In addition, CO2-philic nanodomains in the separation layer were constructed by grafting PEGDA into MXene interlayers, which enhanced the CO2 affinity through the MXene interlayers, while non-CO2-philic nanodomains could promote CO2 transport due to the low resistance. The membrane could exhibit optimal separation performance with a CO2 permeance of 765.5 GPU, a CO2/N2 selectivity of 54.5, and a CO2/CH4 selectivity of 66.2, overcoming the 2008 Robeson upper bounds limitation. Overall, this facile approach endows a precise controlled molecular sieving MXene membrane for superior CO2 separation, which could be applied for interlayer spacing control of other 2D materials during membrane construction.

Recycling the High-Salinity Textile Wastewater by Quercetin-Based Nanofiltration Membranes with Minimal Water and Energy Consumption.

Effective recovery of dyes and salts from textile wastewater by nanofiltration (NF) remains a serious challenge due to the high consumption of water and energy caused by the limited performance of the available membranes. Herein, a novel strategy is described to prepare loose polyester NF membranes by using renewable quercetin as the aqueous monomer for fractionation of high salinity textile wastewater with minimal water and energy consumption. Compared with NF270, taken as the reference membrane, the QE-0.2/TMC-0.2 membrane significantly improved the efficiency for dye/salt fractionation by 288%. The water consumption was also decreased by 42.9%. The efficiency is attributed to an ultrahigh water permeance of 198 ± 2.1 L-1 m-2 h-1 bar-1 with a high selectivity of 123 (extremely low NaCl rejection of 1.6% and high Congo red rejection of 99.2%). The optimal quercetin-based membrane had an ultrathin separation layer of about 39 ± 1.2 nm with good hydrophilicity and negative charge density. Moreover, this work includes a novel method of comparison with a theoretically ideal membrane, which shows that both the energy and water consumption are near their theoretical minimum. This strategy is expected to save energy and minimize carbon emissions for membrane-based wastewater treatment systems.

A Facile and Scalable Fabrication Procedure for Thin-Film Composite Membranes: Integration of Phase Inversion and Interfacial Polymerization.

Conventional dense thin-film composite (TFC) membranes evince a universally low water permeability, the increase of which typically relies on introducing additional transport channels based on intricate steps within a membrane preparation process. In this study, we reported a novel and simplified procedure for the fabrication of high-performance TFC membranes. Specifically, the dissolution of aqueous monomers in the casting solution was utilized for the following interfacial polymerization (IP). Since the monomers diffused to the water bath during phase inversion, the control of precipitation time enabled an effective regulation of the monomer concentration in the formed polymeric substrates, where the IP reaction was initiated by the addition of the organic phase. The entire and uniform embedment of aqueous monomers inside the substrates contributed to the formation of ultrathin and smooth selective layers. An excellent separation performance (i.e., water permeability: 34.7 L m-2 h-1 bar-1; Na2SO4 rejection: ∼96%) could be attained using two types of aqueous monomers (i.e., piperazine and ß-cyclodextrin), demonstrating the effectiveness and universality of this method. Compared to the conventional immersion-based process, this novel procedure shows distinct advantages in reducing monomer usage, shortening the production cycle, and achieving a more superior membrane performance, which is highly promising for large-scale membrane manufacture.

Covalent organic frameworks for membrane separation.

Covalent organic frameworks (COFs), which are constructed from organic linkers, are a new class of crystalline porous materials comprising periodically extended and covalently bound network structures. The intrinsic structures and the tailorable organic linkers endow COFs with a low density, large surface area, tunable pore size and structure, and facilely-tailored functionality, attracting increasing interests in different fields including membrane separations. Exciting research activities ranging from fabrication strategies to separation applications of COF-based membranes have appeared. This review analyzes the synthesis and applications of diverse continuous/discontinuous COF membranes, such as COF-based mixed matrix membranes (MMMs), COF-based thin film nanocomposite (TFN) membranes, and free-standing COF films. Special attention was given to pore size, stability, hydrophilicity/hydrophobicity and surface charge of COFs in view of determining proper COFs for membrane fabrication, along with the approaches to fabricate COF-based membranes, such as blending, in situ growth, layer-by-layer stacking and interfacial polymerization (IP). Moreover, applications of COF-based membranes in gas separation, water treatment (deaslination and dye removal), organic solvent nanofiltration (OSN), pervaporation and fuel cell are disscussed. Finally, we illustrate the advantages and disadvantages of COF-based membranes through a comparison with MOF-based membranes, and the remaining challenges and future opportunities in this field.

Systematic profiling of alternative splicing signature reveals prognostic predictor for ovarian cancer.

OBJECTIVE: The majority of genes are alternatively spliced and growing evidence suggests that alternative splicing is modified in cancer and is associated with cancer progression. Systematic analysis of alternative splicing signature in ovarian cancer is lacking and greatly needed. METHODS: We profiled genome-wide alternative splicing events in 408 ovarian serous cystadenocarcinoma (OV) patients in TCGA. Seven types of alternative splicing events were curated and prognostic analyses were performed with predictive models and splicing network built for OV patients. RESULTS: Among 48,049 mRNA splicing events in 10,582 genes, we detected 2,611 alternative splicing events in 2,036 genes which were significant associated with overall survival of OV patients. Exon skip events were the most powerful prognostic factors among the seven types. The area under the curve of the receiver-operator characteristic curve for prognostic predictor, which was built with top significant alternative splicing events, was 0.937 at 2,000 days of overall survival, indicating powerful efficiency in distinguishing patient outcome. Interestingly, splicing correlation network suggested obvious trends in the role of splicing factors in OV. CONCLUSIONS: In summary, we built powerful prognostic predictors for OV patients and uncovered interesting splicing networks which could be underlying mechanisms.

Synergistic interfacial polymerization between hydramine/diamine and trimesoyl chloride: A novel reaction for NF membrane preparation.

Polyester-amide (PEA) thin film composite (TFC) NF membranes have rapidly evolved towards a competitive performance, benefiting from their remarkable antifouling capability and superior chlorine resistance. In this report, a new concept of synergistic interfacial polymerization is explored, which promptly triggers the reaction between hydramines and trimesoyl chloride (TMC) in the presence of a trace amount of diamines. This rapid-start mode enables the formation of defect-free PEA films without the requirement of catalysis. A comprehensive characterization of physicochemical properties using high-resolution mass spectrometer (HRMS) reveals that the recombination and formation of a "hydramine-diamine" coupling unit plays a decisive role in activating the synergistic interfacial polymerization reaction with TMC molecules. Taking the pair of serinol and piperazine (PIP) as an example, the PEA-NF membrane fabricated with 0.1 w/v% serinol mixed with 0.04 w/v% PIP as water-soluble monomer and 0.1 w/v% TMC as oil phase monomer was found to have a pure water permeability (PWP) of 18.5 L·m-2·h-1·bar-1 and a MgSO4 rejection of 95.5 %, which surpasses almost all the reported PEA NF membranes. Findings of the current research provide more possibilities for the low-cost and rapid synthesis of high-performance PEA membranes aiming for water purification.

AnglesRefine: Refinement of 3D Protein Structures Using Transformer Based on Torsion Angles.

The goal of protein structure refinement is to enhance the precision of predicted protein models, particularly at the residue level of the local structure. Existing refinement approaches primarily rely on physics, whereas molecular simulation methods are resource-intensive and time-consuming. In this study, we employ deep learning methods to extract structural constraints from protein structure residues to assist in protein structure refinement. We introduce a novel method, AnglesRefine, which focuses on a protein's secondary structure and employs transformer to refine various protein structure angles (psi, phi, omega, CA_C_N_angle, C_N_CA_angle, N_CA_C_angle), ultimately generating a superior protein model based on the refined angles. We evaluate our approach against other cutting-edge methods using the CASP11-14 and CASP15 datasets. Experimental outcomes indicate that our method generally surpasses other techniques on the CASP11-14 test dataset, while performing comparably or marginally better on the CASP15 test dataset. Our method consistently demonstrates the least likelihood of model quality degradation, e.g., the degradation percentage of our method is less than 10%, while other methods are about 50%. Furthermore, as our approach eliminates the need for conformational search and sampling, it significantly reduces computational time compared to existing refinement methods.

Wavelet-Guided Promotion-Suppression Transformer for Surface-Defect Detection.

Surface-defect detection aims to accurately locate and classify defect areas in images via pixel-level annotations. Different from the objects in traditional image segmentation, defect areas comprise a small group of pixels with random shapes, characterized by uncommon textures and edges that are inconsistent with the normal surface patterns of industrial products. This task-specific knowledge is hardly considered in the current methods. Therefore, we propose a two-stage "promotion-suppression" transformer (PST) framework, which explicitly adopts the wavelet features to guide the network to focus on the detailed features in the images. Specifically, in the promotion stage, we propose the Haar augmentation module to improve the backbone's sensitivity to high-frequency details. However, the background noise is inevitably amplified as well because it also constitutes high-frequency information. Therefore, a quadratic feature-fusion module (QFFM) is proposed in the suppression stage, which exploits the two properties of noise: independence and attenuation. The QFFM analyzes the similarities and differences between noise and defect features to achieve noise suppression. Compared with the traditional linear-fusion approach, the QFFM is more sensitive to high-frequency details; thus, it can afford highly discriminative features. Extensive experiments are conducted on three datasets, namely DAGM, MT, and CRACK500, which demonstrate the superiority of the proposed PST framework.

When Coordination Polymers Meet Wood: From Molecular Design toward Sustainable Solar Desalination.

Solar-driven interfacial evaporation harnessing solar energy on a water surface provides a sustainable and economic means to efficiently capture freshwater from nontraditional water sources. Endowed with a hierarchical porous structure and mechanical stability, wood-based evaporators represent a renewable alternative to petroleum-based materials. Nonetheless, incidental inferiorities of a low evaporation rate and weak interfacial strength are challenging to overcome. Herein, we propose the usage of chemically stable coordination polymers (Ni-dithiooxamidato, Ni-DTA) as hydrophilic photothermal nanomaterials for the molecular design of robust wood-based evaporators with improved performance. In situ synthesis of Ni-DTA onto the channel wall of balsawood provides sufficient photothermal domains that localize the converted energy for facilitated interfacial evaporation. A rational control of methanol/dimethylformamide ratios enables the coexistence of 1D-nanofibers and 0D-nanoparticles, endowing Balsa-NiDTA with a high evaporation rate of 2.75 kg m-2 h-1 and an energy efficiency of 82% under one-sun illumination. Experimental and simulation results reveal that Ni-DTA polymers with strong hydration ability decrease the equivalent evaporation enthalpy induced by decreased H-bonding density of water molecules near the evaporation interface. The Balsa-NiDTA evaporator showed a high chemical stability, mainly due to the robust Ni-S/Ni-N bonds and the superior cellulose affinity of Ni-DTA. Furthermore, the Balsa-NiDTA evaporator shows an excellent antibacterial activity and low oil-fouling propensity. This work presents a facile and mild strategy to design chemically stable wood-based evaporators, contributing to highly efficient and sustainable solar desalination under harsh conditions.

Covalent Organic Framework-Mediated Thin-Film Composite Polyamide Membranes toward Precise Ion Sieving.

Covalent organic frameworks (COFs) have evinced a potential solution that promises for fast and efficient molecular separation due to the presence of orderly arranged pores and regulable pore apertures. Herein, the synthesized COF (TPB-DMTP-COF) with the pore aperture matching the pore size of the nanofiltration (NF) membrane was utilized to modulate the physicochemical characters of the polyamide (PA) membranes. It is demonstrated that COFs with superior polymer affinity and hydrophilicity not only circumvent the nonselective interfacial cavities but also improve the hydrophilicity of the resultant thin-film nanocomposite (TFN) membranes. Furthermore, the predeposited COF layer is able to slow down the diffusion rate toward the reaction boundary through hydrogen bonding, which is consistent with the results of molecular dynamic (MD) and dissipative particle dynamic (DPD) simulations. In this context, COF-modulated TFN membranes show a roughened and thickened surface with bubble-shaped structures in contrast to the nodular structure of original polyamide membranes. Combined with the introduced in-plane pores of COFs, the resultant TFN membranes display a significantly elevated water permeance of 35.7 L m2 h-1 bar-1, almost 4-fold that of unmodified polyamide membranes. Furthermore, the selectivity coefficient of Cl-/SO42- for COF-modulated TFN membranes achieves a high value of 84 mainly related to the enhanced charge density, far exceeding the traditional NF membranes. This work is considered to provide a guideline of exploring hydrophilic COFs as an interlayer for constructing highly permeable membranes with precise ion-sieving ability.

Microporous organic nanotube assisted design of high performance nanofiltration membranes.

Microporous organic nanotubes (MONs) hold considerable promise for designing molecular-sieving membranes because of their high microporosity, customizable chemical functionalities, and favorable polymer affinity. Herein, we report the use of MONs derived from covalent organic frameworks to engineer 15-nm-thick microporous membranes via interfacial polymerization (IP). The incorporation of a highly porous and interpenetrated MON layer on the membrane before the IP reaction leads to the formation of polyamide membranes with Turing structure, enhanced microporosity, and reduced thickness. The MON-modified membranes achieve a remarkable water permeability of 41.7 L m-2 h-1 bar-1 and high retention of boron (78.0%) and phosphorus (96.8%) at alkaline conditions (pH 10), surpassing those of reported nanofiltration membranes. Molecular simulations reveal that introducing the MONs not only reduces the amine molecule diffusion toward the organic phase boundary but also increases membrane porosity and the density of water molecules around the membrane pores. This MON-regulated IP strategy provides guidelines for creating high-permeability membranes for precise nanofiltration.

A novel ceramic-based thin-film composite nanofiltration membrane with enhanced performance and regeneration potential.

The rational design of a ceramic-based nanofiltration membrane remains a significant challenge due to its performance and fabrication cost. Herein, we report a high-performance ceramic-based thin-film composite (TFC) membrane fabricated via a typical interfacial polymerization on an interwoven net substrate assembled by titanium dioxide (TiO2) nanowires. The chemical properties and morphologies were systematically investigated for ceramic substrates and their corresponding TFC membranes. Due to the significantly improved hydrophilicity of the TiO2 framework, more reactive amine monomers were uniformly adsorbed on the modified surface of the ceramic substrate, yielding an ultrathin polyamide layer with less resistance. In addition, the smooth surface and decreased pore size of the TiO2 framework contributed to forming a defect-free polyamide layer. As a result, the obtained ceramic-based TFC membrane evinced high permeance of 26.4 L m-2 h-1 bar-1 and excellent salt rejection efficiency, leading to simultaneous improvements compared with the control TFC membrane without the TiO2 framework. Notably, the potential regeneration ability of the ceramic-based TFC membrane could be achieved via facile low-temperature calcination and re-polymerization process due to the varied thermostability between the polyamide layer and the robust ceramic substrate. The operation of regeneration helped to prolong the lifetime and decrease the cost for the ceramic-based TFC membrane. This research provides a feasible protocol to fabricate sustainable ceramic-based nanofiltration membranes with enhanced performance for water treatment.

Characteristics of High Suicide Risk Messages From Users of a Social Network-Sina Weibo "Tree Hole".

Background: People with suicidal ideation post suicide-related information on social media, and some may choose collective suicide. Sina Weibo is one of the most popular social media platforms in China, and "Zoufan" is one of the largest depression "Tree Holes." To collect suicide warning information and prevent suicide behaviors, researchers conducted real-time network monitoring of messages in the "Zoufan" tree hole via artificial intelligence robots. Objective: To explore characteristics of time, content and suicidal behaviors by analyzing high suicide risk comments in the "Zoufan" tree hole. Methods: Knowledge graph technology was used to screen high suicide risk comments in the "Zoufan" tree hole. Users' level of activity was analyzed by calculating the number of messages per hour. Words in messages were segmented by a Jieba tool. Keywords and a keywords co-occurrence matrix were extracted using a TF-IDF algorithm. Gephi software was used to conduct keywords co-occurrence network analysis. Results: Among 5,766 high suicide risk comments, 73.27% were level 7 (suicide method was determined but not the suicide date). Females and users from economically developed cities are more likely to express suicide ideation on social media. High suicide risk users were more active during nighttime, and they expressed strong negative emotions and willingness to end their life. Jumping off buildings, wrist slashing, burning charcoal, hanging and sleeping pills were the most frequently mentioned suicide methods. About 17.55% of comments included suicide invitations. Negative cognition and emotions are the most common suicide reason. Conclusion: Users sending high risk suicide messages on social media expressed strong suicidal ideation. Females and users from economically developed cities were more likely to leave high suicide risk comments on social media. Nighttime was the most active period for users. Characteristics of high suicide risk messages help to improve the automatic suicide monitoring system. More advanced technologies are needed to perform critical analysis to obtain accurate characteristics of the users and messages on social media. It is necessary to improve the 24-h crisis warning and intervention system for social media and create a good online social environment.

Suicidal ideation in college students having major depressive disorder: Role of childhood trauma, personality and dysfunctional attitudes.

BACKGROUND: Suicide in college students is a major public health concern. Suicidal ideation (SI) is associated with childhood trauma, personality, dysfunctional attitudes and depressive symptoms, but how they interact to predict SI remains unclear. METHODS: Using cross-sectional design and convenience sampling method, a survey was conducted among 565 college students having major depressive disorder (MDD). The Childhood Trauma Questionnaire, Eysenck Personality Questionnaire, Dysfunctional Attitudes Scale and Hamilton Depression Scale assessed participants' psychosocial factors. Chi-square test, t-test, Pearson correlation, and Structural Equation Model were used in data analysis. RESULTS: Overall, 66.02% of participants with MDD had SI. Those with SI showed significant differences in physical abuse, emotional abuse, physical neglect, emotional neglect, psychoticism, neuroticism, extroversion, dysfunctional attitudes and depressive symptoms compared with those without SI. Childhood trauma, psychoticism, neuroticism, extroversion and dysfunctional attitudes affected SI through chain mediation. In addition, depressive symptoms, psychoticism, neuroticism and extroversion directly affected SI. LIMITATIONS: The convenience sampling method may limit the generalizability of the findings. Results may be biased due to the self-report nature of the data collection procedure, the number of research subjects and differences in suicide risk assessment. The cross-sectional study cannot be used to infer causality. CONCLUSIONS: The factors of childhood trauma, personality and dysfunctional attitudes affect SI through chain mediation. In addition, depressive symptoms and personality independently predict the occurrence of SI.

Acid Hydrotropic Fractionation of Lignocelluloses for Sustainable Biorefinery: Advantages, Opportunities, and Research Needs.

This Minireview provides a comprehensive discussion on the potential of using acid hydrotropes for sustainably fractionating lignocelluloses for biorefinery applications. Acid hydrotropes are a class of acids that have hydrotrope properties toward lignin, which helps to solubilize lignin in aqueous systems. With the capability of cleaving ether and ester bonds and even lignin-carbohydrate complex (LCC) linkages, these acid hydrotropes can therefore isolate lignin embedded in the plant biomass cell wall and subsequently solubilize the isolated lignin in aqueous systems. Performances of two acid hydrotropes, that is, an aromatic sulfonic acid [p-toluenesulfonic acid (p-TsOH)] and a dicarboxylic acid [maleic acid (MA)], in terms of delignification and dissolution of hemicelluloses, and reducing lignin condensation, were evaluated and compared. The advantages of lignin esterification by MA for producing cellulosic sugars through enzymatic hydrolysis and lignin-containing cellulose nanofibrils (LCNFs) through mechanical fibrillation from the fractionated water insoluble solids (WIS), and for obtaining less condensed lignin with light color, were demonstrated. The excellent enzymatic digestibility of maleic acid hydrotropic fractionation WISs was also demonstrated by comparing with WISs from other fractionation processes. The recyclability and reusability of acid hydrotropes were also reviewed. Finally, perspectives on future research needs to address key technical issues for commercialization were also provided.

PIK3CA mutation confers resistance to chemotherapy in triple-negative breast cancer by inhibiting apoptosis and activating the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer, the main treatments for which are chemotherapy and surgery. PIK3CA is an oncogene that encodes the p110α subunit of class IA PI3K to regulate cell proliferation and apoptosis. Some reports have observed neoadjuvant chemotherapy (NAC) to have poor pathological complete response (pCR) rates in TNBC with PIK3CA mutation. This study aimed to explore the mechanism of how mutant PIK3CA alters chemotherapeutic susceptibility in TNBC. METHODS: TNBC cell lines (MDA-MB-231 and MDA-MB-468) with PIK3CA gene mutations (E545K and H1047R regions) and overexpression were established by transfection. NOD/SCID mice were used for in vivo experiments. Epirubicin was used as the chemotherapeutic agent. Cell viability, cell cycle, apoptosis, and Transwell assays were conducted for phenotype analysis. Western blot, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry were used to detect gene and protein expression levels. A clinical analysis of 50 patients with TNBC was also performed. RESULTS: Cell viability and Transwell assays showed that PIK3CA mutation promoted TNBC cell growth and conferred an enhanced migratory phenotype. Cell cycle and apoptosis assays showed that PIK3CA mutation moderately improved the proliferation ability of TNBC cells and remarkably inhibited their apoptosis. After epirubicin therapy, the proportion of early apoptotic cells decreased among cells with PIK3CA mutation. Further, xenograft tumors grew faster in NOD/SCID mice injected with mutated cell lines than in control group, suggesting that PIK3CA mutation caused chemotherapy resistance. Importantly, western blot and immunohistochemical analysis showed that cells and mouse tumors in the PIK3CA mutation groups exhibited different expression levels of apoptosis-related markers (Xiap, Bcl-2, and Caspase 3) and proteins associated with the PI3K/AKT/mTOR pathway (p110α, AKT, p-AKT, mTOR, p-mTOR, p-4E-BP1, p-p70S6K, and Pten). Moreover, prognostic analysis of 50 patients with TNBC indicated that PIK3CA mutation might be linked with relapse and death. CONCLUSIONS: PIK3CA mutation confers resistance to chemotherapy in TNBC by inhibiting apoptosis and activating the PI3K/AKT/mTOR signaling pathway.

Comparative healing of swine skin following incisions with different surgical devices.

BACKGROUND: Electrosurgical technology is widely used in surgical dissection and hemostasis, but the generated heat creates thermal injury to adjacent tissues and delays wound healing. The plasma blade (PB) applies pulsed radiofrequency (RF) to generate electrical plasma along the edge of a thin, flat, insulated electrode, minimizing collateral tissue damage. This study aimed to evaluate wound healing in swine skin following incision with a new surgical system that applies low-temperature plasma (NTS-100), a foreign PB, conventional electrosurgery (ES), and a scalpel blade. METHODS: In vitro porcine skin and an in vivo porcine skin model were used in this study. Full-thickness skin incisions 3 cm in length were made on the dorsum of each animal for each of the 5 surgical procedures at 0, 21, 28, 35, and 42 days. The timing of the surgical procedures allowed for wound-healing data points at 1, 2, 3, and 6 weeks accordingly. Local operating temperature and blood loss were quantified. Wounds were harvested at designated time points, tested for wound tensile strength, and examined histologically for scar formation and tissue damage. RESULTS: Local operating temperature was reduced significantly with NTS-100 (cut mode 83.12±23.55 °C; coagulation mode 90.07±10.6 °C) compared with PB (cut mode 94.46±11.48 °C; coagulation mode 100.23±6.58 °C, P<0.05) and ES (cut mode 208.99±34.33 °C, P<0.01; coagulation mode 233.37±28.69 °C, P<0.01) in vitro. Acute thermal damage from NTS-100 was significantly less than ES incisions (cut mode: 247.345±42.274 versus 495.295±103.525 µm, P<0.01; coagulation mode: 351.419±127.948 versus 584.516±31.708 µm, P<0.05). Bleeding, histological scoring of injury, and wound strength were equivalent for the NTS-100 and PB incisions. CONCLUSIONS: The local operating temperature of NTS-100 was lower than PB, and NTS-100 had similarly reliable safety and efficacy.

Flexible Aliphatic-Aromatic Polyamide Thin Film Composite Membrane for Highly Efficient Organic Solvent Nanofiltration.

Membranes with strong solvent resistance and efficient molecular separation are desirable in industries. Especially the fractionation of organic molecules in harsh organic solvents still remains a challenge in the pharmaceutical industry. Here, we report a flexible aliphatic-aromatic polyamide thin-film composite (TFC) membrane with high stability, permeability, and precise selectivity in mild solvents as well as in polar aprotic solvents. This composite organic solvent nanofiltration (OSN) membrane integrates a cross-linked sub-100 nm nanofilm and a nanofibrous sublayer. The flexible aliphatic chains in the polyamide network render the selective layer with a tunable free volume in different organic solvents. Consistent with the solvent swelling degrees, the membrane shows a cutoff in a sequence of dimethyl sulfoxide (DMSO, MWCO: 814 g mol-1) > N,N-dimethylformamide (DMF, MWCO: 648 g mol-1) > methanol (MWCO: 506 g mol-1, with DMF activation) > methanol (MWCO: 327 g mol-1). The membrane can precisely fractionate two molecules with difference in molar mass of <166 g mol-1 in a polar aprotic solvent, DMSO. Long-term filtration tests in DMF further demonstrate that the TFC membrane has an outstanding chemical stability and molecular selectivity in aggressive organic media. This work provides an efficient way to control OSN membrane separations by introducing flexible alkane chains into the rigid polymer structure followed by solvent activation. Additionally, the high permeance and excellent separation efficiency of the TFC membrane highlight its great potential for molecular separation in pharmaceutical and chemical industries.