Case report: ATM A1159T mutation in malignant peritoneal mesothelioma may be associated with tumor recurrence.

Malignant peritoneal mesothelioma is an exceedingly rare malignant tumor. Herein, we present a case of malignant peritoneal mesothelioma in a 59-year-old Chinese female patient who was stable after treatment for multiple relapses. Imaging revealed massive ascites and an irregular thickening of the peritoneal mesangium. Laparoscopic biopsy revealed heterogeneous cell nests in the parietal peritoneal fibrous tissue, which were confirmed by immunohistochemical staining for Calretinin, WT-1, and D2-40. In terms of genetic screening, BAP1, CSF1R, and other key driver gene variants closely related to malignant peritoneal mesothelioma have been explored in tumor tissues. Notably, CARD11 driver mutation was first found in all malignant peritoneal mesothelioma patients, and ATM A1159T gene mutation found in recurrent focal tissue may be associated with recurrent tumor recurrence.

Carboxylated mesoporous silica nanoparticle-nucleic acid chimera conjugate-assisted delivery of siRNA and doxorubicin effectively treat drug-resistant bladder cancer.

Chemotherapy is the main treatment for bladder cancer, but drug resistance and side effects limit its application and therapeutic effect. Herein, we constructed doxorubicin (DOX)/COOH-mesoporous silica nanoparticle/polyethylenimine (PEI)/nucleic acid chimeras (DOX/MSN/Chimeras) to reduce the toxicity of chemotherapy drugs and the resistance of bladder cancer cells. Transmission electron microscopy showed that PEI was coated on the DOX/MSN/BSA nanoparticles with a diameter of about 150 nm. DOX/MSN/PEI could control DOX release for over 48 h, and the sudden release rate was significantly lower than DOX/MSN. Immunohistochemical results showed that DOX/MSN/Chimera specifically bound to bladder cancer cells, and markedly inhibited PI3K expression and proliferation of DOX-resistant bladder cancer cells. DOX/MSN/Chimera promoted the apoptosis of drug-resistant bladder cancer cells, which was superior to DOX/MSN/Aptamer or DOX/MSN. We further carried out animal experiments and found that DOX/MSN/Chimera could reduce the volume of transplanted tumors in vivo. Compared with DOX/MSN/Aptamer group, the proliferation rate was significantly decreased and the proportion of apoptotic cells was highly increased. Through the histological observation of kidneys and lungs, we believed that DOX/MSN/Chimera can effectively reduce the damage of chemotherapy drugs to normal tissues. In conclusion, we constructed a COOH-MSN/nucleic acid chimera conjugate for the targeted delivery of siRNA and anti-cancer drugs. Our study provides a new method for personalized and targeted treatment of drug-resistant bladder cancer.

Transient Response and Ionic Dynamics in Organic Electrochemical Transistors.

The rapid development of organic electrochemical transistors (OECTs) has ushered in a new era in organic electronics, distinguishing itself through its application in a variety of domains, from high-speed logic circuits to sensitive biosensors, and neuromorphic devices like artificial synapses and organic electrochemical random-access memories. Despite recent strides in enhancing OECT performance, driven by the demand for superior transient response capabilities, a comprehensive understanding of the complex interplay between charge and ion transport, alongside electron-ion interactions, as well as the optimization strategies, remains elusive. This review aims to bridge this gap by providing a systematic overview on the fundamental working principles of OECT transient responses, emphasizing advancements in device physics and optimization approaches. We review the critical aspect of transient ion dynamics in both volatile and non-volatile applications, as well as the impact of materials, morphology, device structure strategies on optimizing transient responses. This paper not only offers a detailed overview of the current state of the art, but also identifies promising avenues for future research, aiming to drive future performance advancements in diversified applications.

Minocycline Inhibits Tick-Borne Encephalitis Virus and Protects Infected Cells via Multiple Pathways.

Tick-borne Encephalitis (TBE) is a zoonotic disease caused by the Tick-borne Encephalitis virus (TBEV), which affects the central nervous system of both humans and animals. Currently, there is no specific therapy for patients with TBE, with symptomatic treatment being the primary approach. In this study, the effects of minocycline (MIN), which is a kind of tetracycline antibiotic, on TBEV propagation and cellular protection in TBEV-infected cell lines were evaluated. Indirect immunofluorescence, virus titers, and RT-qPCR results showed that 48 h post-treatment with MIN, TBEV replication was significantly inhibited in a dose-dependent manner. In addition, the inhibitory effect of MIN on different TBEV multiplicities of infection (MOIs) in Vero cells was studied. Furthermore, the transcriptomic analysis and RT-qPCR results indicate that after incubation with MIN, the levels of TBEV and CALML4 were decreased, whereas the levels of calcium channel receptors, such as RYR2 and SNAP25, were significantly increased. MIN also regulated MAPK-ERK-related factors, including FGF2, PDGFRA, PLCB2, and p-ERK, and inhibited inflammatory responses. These data indicate that administering MIN to TBEV-infected cells can reduce the TBEV level, regulate calcium signaling pathway-associated proteins, and inhibit the MAPK-ERK signaling pathway and inflammatory responses. This research offers innovative strategies for the advancement of anti-TBEV therapy.

Multiresponsive Bilayer Hydrogel Actuator with Switchable Shape Morphing Capability and Visible Color/Fluorescence Change.

Bilayer hydrogels, endowed with multiresponsive and switchable color-changing properties, have garnered significant attention for bioinspired artificial intelligent materials. However, the design and fabrication of such hydrogels that can fully mimic the adaptation of the live organism, i.e., simultaneous changes in shape, fluorescent, and/or visible color, still remain significant challenges. Herein, a multiresponsive (e.g., temperature, salt, and pH) and multiadaptive (shape, fluorescent color, and visible color changes) hydrogel was fabricated by employing monomers featuring pH-responsive fluorescence 4-(2-(4-(dimethylamino) phenyl)-1-isocyanovinyl) phenol (DP) and switchable color-changing 4-(2-sulfethyl) -1-(4-vinylbenzyl) pyridinium betaine (VPES). The bilayer hydrogel comprises a temperature- and pH-responsive gel layer, poly(N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate), along with a pH-, temperature-, and salt-responsive gel layer, poly(acrylamide-co-2-(dimethylamino)ethyl methacrylate-co-VPES)@DP. Due to the opposite swelling/shrinking behavior between the two layers, the prepared hydrogel exhibits shape changes in response to thermal, salt, and pH stimuli, along with switchable fluorescent color and visible color change that originate from DP and polyVPES, respectively. Apart from multiresponsive behavior, this hydrogel also shows an excellent antifatigue property and high sensitivity, which makes it hold significant potential in many applications. We anticipate that this strategy to realize multiresponsive capability in this work can also inspire the design of the biomimetic smart materials.

[Air Pollutant Spatiotemporal Evolution Characteristics and Effects on Human Health in Xi'an City].

Xi'an is the political, economic, and cultural center of northwest China with a developed industry. Air pollution incidents have brought great challenges to the high-quality development of the social economy. It is vital to study air pollution characteristics and clarify their impact on human health. In this study, we first analyzed the spatiotemporal variations in air pollutants in the study region from 2015 to 2021. Then, the air quality index (AQI), aggregate air quality index (AAQI), and health risk-based air quality index (HAQI) were used to assess health risks. Based on these, the AirQ2.2.3 model was used to quantify health effects. The results showed that the major pollutants were PM10, PM2.5, and O3. The main pollution characteristics of the study area were terrain characteristics and the mixed pollution of anthropogenic emissions. Compared to that of AQI, AAQI and HAQI showed better classification performance for pollution levels. HAQI revealed that approximately 80 % of the population was exposed to unhealthy air throughout the year in the study region. People were most exposed to unhealthy air in winter, followed by autumn and spring, and the least in summer. The AirQ2.2.3 model quantified the total mortality proportions attributable to PM2.5, PM10, SO2, CO, NO2, and O3, which were 0.99 %, 2.04 %, 0.41 %, 1.72 %, 8.76 %, and 3.67 %, respectively. The attributable proportion of mortality of the respiratory system and cardiovascular diseases was consistent with the change rule of total mortality.

Unlocking the Potential of CO2 Capture: A Synergistic Hybridization Strategy for Polymeric Hydrogels with Tunable Physicochemical Properties.

Unlocking CO2 capture potential remains a complex and challenging endeavor. Here, a blueprint is crafted for optimizing materials through CO2 capture and developing a synergistic hybridization strategy that involves synthesizing CO2-responsive hydrogels by integrating polymeric networks interpenetrated with polyethyleneimine (PEI) chains and inorganic CaCl2. Diverging from conventional CO2 absorbents, which typically serve a singular function in CO2 capture, these hybrid PEAC hydrogels additionally harness its presence to tune their optical and mechanical properties once interacting with CO2. Such synergistic functions entail two significant steps: (i) rapid CO2-fixing through PEI chains to generate abundant carbamic acid and carbamate species and (ii) mineralization via CaCl2 to induce the formation of CaCO3 micro-crystals within the hydrogel matrix. Due to the reversible bonding, the PEAC hydrogels enable the decoupling of CO2 through an acid fumigation treatment or a heating process, achieving dynamic CO2 capture-release cycles up to 8 times. Furthermore, the polyethyleneimine-acrylamide-calcium chloride (PEAC) hydrogel exhibits varying antibacterial attributes and high interfacial adhesive strength, which can be modulated by fine-tuning the compositions of PEI and CaCl2. This versatility underscores the promising potential of PEAC hydrogels, which not only unlocks CO2 capture capabilities but also offers opportunities in diverse biological and biomedical applications.

The deregulation of arachidonic acid metabolism in ovarian cancer.

Arachidonic acid (AA) is a crucial polyunsaturated fatty acid in the human body, metabolized through the pathways of COX, LOX, and cytochrome P450 oxidase to generate various metabolites. Recent studies have indicated that AA and its metabolites play significant regulatory roles in the onset and progression of ovarian cancer. This article examines the recent research advancements on the correlation between AA metabolites and ovarian cancer, both domestically and internationally, suggesting their potential use as biological markers for early diagnosis, targeted therapy, and prognosis monitoring.

Construction of aptamer-siRNA chimera and glutamine modified carboxymethyl-ß-cyclodextrin nanoparticles for the combination therapy against lung squamous cell carcinoma.

Combination therapy has become the most important treatment for advanced non-small cell lung cancer (NSCLC), which can significantly improve the prognosis of patients. However, poor targeting and adverse reactions limited its clinical application. Here, we constructed an AS1411 aptamer-programmed cell death ligand-1 (PD-L1) siRNA chimera/polyethylenimine/glutamine/ß-cyclodextrin/doxorubicin (Chimera/ PEI/Gln/ß-CD/DOX) nanoparticle for the combination therapy (chemotherapy combined with immunotherapy). Scanning electron microscopy showed that PEI/Gln/ß-CD/DOX nanoparticle was conical, with a diameter of about 250-500 nm. AS1411 aptamer-PD-L1 siRNA chimera can effectively bind NSCLC cells and inhibit PD-L1 expression, further activating T cells and CD8+T cells. Glutamine modification effectively promoted the doxorubicin uptake by cancer cells and induced their apoptosis. Animal experiments showed that our nanoparticles effectively treated the transplanted tumor, and the adverse reactions were reduced. Compared with the Aptamer/ß-CD/DOX group, the volume and ki-67 index of transplanted tumors in the Chimera/ß-CD/DOX group were significantly decreased, while the apoptosis ratio was increased. Immunohistochemical results showed that Compared with the Aptamer/ß-CD/DOX group, the number of T cells and CD8+T cells in the Chimera/ß-CD/DOX group was increased by 1.34 and 1.41 times. Glutamine modification enhanced the chemotherapeutic efficacy and anti-tumor immune response in vivo. Our study provided a new method for the combination therapy of lung squamous cell carcinoma.

Chemoenzymatic Installation of Site-Specific Chemical Groups on DNA Enhances the Catalytic Activity.

Functional DNAs are valuable molecular tools in chemical biology and analytical chemistry but suffer from low activities due to their limited chemical functionalities. Here, we present a chemoenzymatic method for site-specific installation of diverse functional groups on DNA, and showcase the application of this method to enhance the catalytic activity of a DNA catalyst. Through chemoenzymatic introduction of distinct chemical groups, such as hydroxyl, carboxyl, and benzyl, at specific positions, we achieve significant enhancements in the catalytic activity of the RNA-cleaving deoxyribozyme 10-23. A single carboxyl modification results in a 100-fold increase, while dual modifications (carboxyl and benzyl) yield an approximately 700-fold increase in activity when an RNA cleavage reaction is catalyzed on a DNA-RNA chimeric substrate. The resulting dually modified DNA catalyst, CaBn, exhibits a kobs of 3.76 min-1 in the presence of 1 mM Mg2+ and can be employed for fluorescent imaging of intracellular magnesium ions. Molecular dynamics simulations reveal the superior capability of CaBn to recruit magnesium ions to metal-ion-binding site 2 and adopt a catalytically competent conformation. Our work provides a broadly accessible strategy for DNA functionalization with diverse chemical modifications, and CaBn offers a highly active DNA catalyst with immense potential in chemistry and biotechnology.

Diversity of evolution in MDR monophasic S. Typhimurium among food animals and food products in Southern China from 2011 to 2018.

The monophasic variant of Salmonella enterica serovar Typhimurium with the antigenic formula 1,4,[5],12:i:- is one of the most common pathogenic bacteria causing global food-borne outbreaks. However, the research on molecular characteristics and evolution of monophasic S. typhimurium in China is still lacking. In the current study, 59 monophasic S. typhimurium strains were isolated from food animals and food products in South China between 2011 and 2018. A total of 87.5 % of monophasic S. typhimurium isolates were grouped into one independent clade with other monophasic S. typhimurium strains in China distinct from other countries by phylogenomic analysis. These isolates possess variable genotypes, including multiple ARGs on plasmid IncHI2, diverse evolutions at the fljAB locus, and virulence factors. Our results suggest that the monophasic S. typhimurium isolates currently circulating in China might be an independent epidemic subtype.

Parallel auxin transport via PINs and plasmodesmata during the Arabidopsis leaf hyponasty response.

KEY MESSAGE: The leaf hyponasty response depends on tip-to-petiole auxin transport. This transport can happen through two parallel pathways: active trans-membrane transport mediated by PIN proteins and passive diffusion through plasmodesmata. A plant's ability to counteract potential shading by neighboring plants depends on transport of the hormone auxin. Neighbor sensing at the leaf tip triggers auxin production. Once this auxin reaches the abaxial petiole epidermis, it causes cell elongation, which leads to leaf hyponasty. Two pathways are known to contribute to this intercellular tip-to-petiole auxin movement: (i) transport facilitated by plasma membrane-localized PIN auxin transporters and (ii) diffusion enabled by plasmodesmata. We tested if these two modes of transport are arranged sequentially or in parallel. Moreover, we investigated if they are functionally linked. Mutants in which one of the two pathways is disrupted indicated that both pathways are necessary for a full hyponasty response. Visualization of PIN3-GFP and PIN7-GFP localization indicated PIN-mediated transport in parallel to plasmodesmata-mediated transport along abaxial midrib epidermis cells. We found plasmodesmata-mediated cell coupling in the pin3pin4pin7 mutant to match wild-type levels, indicating no redundancy between pathways. Similarly, PIN3, PIN4 and PIN7 mRNA levels were unaffected in a mutant with disrupted plasmodesmata pathway. Our results provide mechanistic insight on leaf hyponasty, which might facilitate the manipulation of the shade avoidance response in crops.

Characterization of the physicochemical Properties, bacterial community and non-volatile profiles of fermented Yu jiangsuan by Weissella cibaria and Lactobacillus plantarum.

Yu jiangsuan (YJS) is a unique traditional fermented condiment in China. Physicochemical, bacterial communities, and non-volatile properties were examined in inoculation Autochthonous Weissella cibaria and Lactobacillus plantarum. The results indicated that inoculation samples did well in shortening fermentation time; amino acid nitrogen (AN) and TCA-soluble peptide contents of fermented YJS were 10.8% and 17.4% higher than those of naturally fermented YJS, respectively. However, its total volatile base nitrogen (TVB-N), thiobarbituric acid (TBARS), and nitrite were only 74.3%, 87.2% and 83.6% of those of naturally fermented YJS. In addition, the dominant bacterial genera were Lactobacillus, Weissella and Pectobacterium, whose contributions were 41.2%, 20.3% and 5.5%, respectively. Moreover, 26 significantly differential metabolites were identified, and involved in 10 metabolic pathways. The decomposition of substrates and the formation of differential metabolites in YJS were primarily centered on the TCA cycle and the metabolism of carbohydrates. Therefore, this study is conducive to discovering the bacterial community structure and metabolite composition of probiotic inoculated YJS fermentation, as well as the potential value of core functional bacteria genera in controlling YJS production in industry.

In Situ Growth of Functional Hydrogel Coatings by a Reactive Polyurethane for Biomedical Devices.

Surface modification of thermoplastic polyurethane (TPU) could significantly enhance its suitability for biomedical devices and public health products. Nevertheless, customized modification of polyurethane surfaces with robust interfacial bonding and diverse functions via a simple method remains an enormous challenge. Herein, a novel thermoplastic polyurethane with a photoinitiated benzophenone unit (BPTPU) is designed and synthesized, which can directly grow functional hydrogel coating on polyurethane (PU) in situ by initiating polymerization of diverse monomers under ultraviolet irradiation, without the involvement of organic solvent. The resulting coating not only exhibits tissue-like softness, controllable thickness, lubrication, and robust adhesion strength but also provides customized functions (i.e., antifouling, stimuli-responsive, antibacterial, and fluorescence emission) to the original passive polymer substrates. Importantly, BPTPU can be blended with commercial TPU to produce the BPTPU-based tube by an extruder. Only a trace amount of BPTPU can endow the tube with good photoinitiated capacity. As a proof of concept, the hydrophilic hydrogel-coated BPTPU is shown to mitigate foreign body response in vivo and prevent thrombus formation in rat blood circulation without anticoagulants in vitro. This work offers a new strategy to guide the design of functional polyurethane, an elastomer-hydrogel composite, and holds great prospects for clinical translation.

Editorial for Special Issue: Advances in Smart and Tough Hydrogels.

Smart hydrogels possess both intelligent and responsive properties, which are designed to exhibit specific responses to external stimuli such as changes in temperature, pH, or the presence of specific ions/counterions, making them "smart" or "responsive" materials [...].

Deposition and water repelling of temperature-responsive nanopesticides on leaves.

Pesticides are widely used to increase agricultural productivity, however, weak adhesion and deposition lead to low efficient utilization. Herein, we prepare a nanopesticide formulation (tebuconazole nanopesticides) which is leaf-adhesive, and water-dispersed via a rapid nanoparticle precipitation method, flash nanoprecipitation, using temperature-responsive copolymers poly-(2-(dimethylamino)ethylmethylacrylate)-b-poly(ε-caprolactone) as the carrier. Compared with commercial suspensions, the encapsulation by the polymer improves the deposition of TEB, and the contact angle on foliage is lowered by 40.0°. Due to the small size and strong van der Waals interactions, the anti-washing efficiency of TEB NPs is increased by 37% in contrast to commercial ones. Finally, the acute toxicity of TEB NPs to zebrafish shows a more than 25-fold reduction as compared to commercial formulation indicating good biocompatibility of the nanopesticides. This work is expected to enhance pesticide droplet deposition and adhesion, maximize the use of pesticides, tackling one of the application challenges of pesticides.

A spine segmentation method based on scene aware fusion network.

BACKGROUND: Intervertebral disc herniation, degenerative lumbar spinal stenosis, and other lumbar spine diseases can occur across most age groups. MRI examination is the most commonly used detection method for lumbar spine lesions with its good soft tissue image resolution. However, the diagnosis accuracy is highly dependent on the experience of the diagnostician, leading to subjective errors caused by diagnosticians or differences in diagnostic criteria for multi-center studies in different hospitals, and inefficient diagnosis. These factors necessitate the standardized interpretation and automated classification of lumbar spine MRI to achieve objective consistency. In this research, a deep learning network based on SAFNet is proposed to solve the above challenges. METHODS: In this research, low-level features, mid-level features, and high-level features of spine MRI are extracted. ASPP is used to process the high-level features. The multi-scale feature fusion method is used to increase the scene perception ability of the low-level features and mid-level features. The high-level features are further processed using global adaptive pooling and Sigmoid function to obtain new high-level features. The processed high-level features are then point-multiplied with the mid-level features and low-level features to obtain new high-level features. The new high-level features, low-level features, and mid-level features are all sampled to the same size and concatenated in the channel dimension to output the final result. RESULTS: The DSC of SAFNet for segmenting 17 vertebral structures among 5 folds are 79.46 ± 4.63%, 78.82 ± 7.97%, 81.32 ± 3.45%, 80.56 ± 5.47%, and 80.83 ± 3.48%, with an average DSC of 80.32 ± 5.00%. The average DSC was 80.32 ± 5.00%. Compared to existing methods, our SAFNet provides better segmentation results and has important implications for the diagnosis of spinal and lumbar diseases. CONCLUSIONS: This research proposes SAFNet, a highly accurate and robust spine segmentation deep learning network capable of providing effective anatomical segmentation for diagnostic purposes. The results demonstrate the effectiveness of the proposed method and its potential for improving radiological diagnosis accuracy.

Metformin combined with glucose starvation synergistically suppress triple-negative breast cancer by enhanced unfolded protein response.

Metformin (MET) is a well-documented drug used in the treatment of type II diabetes. Recent studies have revealed its potential anti-tumor effects in various types of cancer. However, the dosage of MET required to exhibit anti-tumor activity is considerably higher than the clinically recommended dosage. In this study, we investigated the synergistical anti-tumor effect of glucose deprivation and MET in MDA-MB-231 cells, which represents a triple-negative breast cancer subtype (TNBC). Our findings demonstrate that glucose deprivation significantly enhances the anti-tumor activity of MET by reducing cell proliferation and increasing cell apoptosis. RNA-seq was performed to identify the key molecules involved in this process. Our results indicate that unfolded protein response of endoplasmic reticulum (UPRER) was significantly activated upon glucose starvation combining with MET compared to glucose starvation alone. Notably, the combined treatment significantly activated UPRER signaling pathway through ATF4/ATF3/CHOP axis, due to enhanced UPRER stress. In conclusion, our study suggests that the synergistic effects of MET and glucose deprivation suppress cell proliferation in TNBC by activating pro-apoptotic molecules through UPRER stress. These findings have potential implications for the anti-tumor application of MET in TNBC.

Zwitterionic nanocapsule-based wound dressing with the function of gradient release of multi-drugs for efficient wound healing.

Efficient wound healing has attracted great interest due to the prevalence of skin damage. It is still highly desired yet challenging to construct a multi-drug loaded wound dressing that can release different drugs at different times to meet specific requirements towards different healing stages. Herein, a wound dressing was developed based on thermoresponsive zwitterionic nanocapsules (ZNs) that were sandwiched between two double-layered fabrics to regulate the multiple drug release pathway. The salt-response of the obtained ZNs was greatly suppressed while its transition temperature was regulated to be ∼37 °C to fit the needs of the physiological environment. Two bioactive substances, human basic fibroblast growth factor (bFGF) for tissue regeneration and norfloxacin for anti-inflammation, were loaded in the ZNs and on the surface of fabrics, respectively, to achieve separative gradient release. The in vitro drug release tests revealed that norfloxacin could be released relatively fast (∼24 h) while the release rate of bFGF was much slower (∼168 h), matching the specific time requirements of inflammation and proliferation stages very well. The in vivo wound healing experiment also confirmed the high wound healing efficiency of the wound dressing developed here, compared to the wound dressings without gradient release characteristics. We believe the strategy illustrated here will provide new insights into the design and biomedical applications of zwitterionic nanocapsules.