Protein purification via consecutive histidine-polyphosphate interaction.

While nickel-nitrilotriacetic acid (Ni-NTA) has greatly advanced recombinant protein purification, its limitations, including nonspecific binding and partial purification for certain proteins, highlight the necessity for additional purification such as size exclusion and ion exchange chromatography. However, specialized equipment such as FPLC is typically needed but not often available in many laboratories. Here, we show a novel method utilizing polyphosphate (polyP) for purifying proteins with histidine repeats via non-covalent interactions. Our study demonstrates that immobilized polyP efficiently binds to histidine-tagged proteins across a pH range of 5.5-7.5, maintaining binding efficacy even in the presence of reducing agent DTT and chelating agent EDTA. We carried out experiments of purifying various proteins from cell lysates and fractions post-Ni-NTA. Our results demonstrate that polyP resin is capable of further purification post-Ni-NTA without the need for specialized equipment and without compromising protein activity. This cost-effective and convenient method offers a viable approach as a complementary approach to Ni-NTA.

Fabrication of polymeric microspheres for biomedical applications.

Polymeric microspheres (PMs) have attracted great attention in the field of biomedicine in the last several decades due to their small particle size, special functionalities shown on the surface and high surface-to-volume ratio. However, how to fabricate PMs which can meet the clinical needs and transform laboratory achievements to industrial scale-up still remains a challenge. Therefore, advanced fabrication technologies are pursued. In this review, we summarize the technologies used to fabricate PMs, including emulsion-based methods, microfluidics, spray drying, coacervation, supercritical fluid and superhydrophobic surface-mediated method and their advantages and disadvantages. We also review the different structures, properties and functions of the PMs and their applications in the fields of drug delivery, cell encapsulation and expansion, scaffolds in tissue engineering, transcatheter arterial embolization and artificial cells. Moreover, we discuss existing challenges and future perspectives for advancing fabrication technologies and biomedical applications of PMs.

Discovery of a Meisoindigo-Derived PROTAC as the ATM Degrader: Revolutionizing Colorectal Cancer Therapy via Synthetic Lethality with ATR Inhibitors.

Meisoindigo (Mei) has long been recognized in chronic myeloid leukemia (CML) treatment. To elucidate its molecular target and mechanisms, we embarked on designing and synthesizing a series of Mei-derived PROTACs. Through this endeavor, VHL-type PROTAC 9b was identified to be highly cytotoxic against SW620, SW480, and K562 cells. Employing DiaPASEF-based quantitative proteomic analysis, in combination with extensive validation assays, we unveiled that 9b potently and selectively degraded ATM across SW620 and SW480 cells in a ubiquitin-proteasome-dependent manner. 9b-induced selective ATM degradation prompted DNA damage response cascades, thereby leading to the cell cycle arrest and cell apoptosis. This pioneering discovery renders the advent of ATM degradation for anti-cancer therapy. Notably, 9b-induced ATM degradation synergistically enhanced the efficacy of ATR inhibitor AZD6738 both in vitro and in vivo. This work establishes the synthetic lethality-inducing properties of ATR inhibitors in the ATM-deficient context, thereby providing new avenues to innovative therapies for colorectal cancer.

Negative pressure pulmonary edema after laparoscopic cholecystectomy: A case report and literature review.

RATIONALE: Negative pressure pulmonary edema (NPPE) is an acute onset of non-cardiogenic interstitial pulmonary edema, commonly seen among surgical patients after extubation from general aneasthesia. It is mainly caused by rapid inspiration with acute upper airway obstruction resulting in significant negative thoracic pressure. PATIENT CONCERNS: A 24-year-old female patient who underwent laparoscopic cholecystectomy under general anesthesia and developed NPPE postoperatively. DIAGNOSES: Her main clinical manifestation was coughing up pink foamy sputum; postoperative CT showed increased texture in both lungs and bilateral ground glass opacities. INTERVENTIONS: Diuretics and steroids were used, and symptomatic supportive treatments such as oxygen were given. OUTCOMES: After treatment, on the fourth post-operative day, her symptoms were relieved and her vital signs were stable enough for her to be discharged. LESSONS: Although this is a rare and severe complication, the prognosis of NPPE is good when it is managed with proper diagnosis and treatment.

Numerical Simulation and Parameter Optimization for Water-to-CO2 Flooding in a Strongly Water-Sensitive Reservoir.

Carbon dioxide flooding can accelerate the development of low-permeability reservoirs of the Kexia group in the K region of the T oil field, thus resolving the issue of inadequate water drive effects. This study was focused on the well group 80513 in the K region, and based on the reservoir and fluid parameters, a simulation model of water-sensitive post-CO2 flooding was constructed to refine the gas injection strategy gradually. The injection rate of the continuous gas injection stage was preferred based on the degree of recovery. Multiindicator and multifactor injection and extraction schemes were established to optimize and analyze the key controlling factors, including the gas injection rate, gas injection period, gas-to-water ratio, and bottom-hole flow pressure, in the carbon dioxide gas-to-water alternation process. Recovery efficiency, oil exchange rate, formation pressure, and carbon dioxide storage rate were used as indicators. After 5 years of continuous CO2 flooding, the results indicated that switching to CO2 gas-water alternating flooding was more appropriate for the target block's environment. The best development plan was achieved when the gas injection rates were 1.0 and 1.25 × 104 m3·d-1 for continuous gas injection and CO2 gas-water alternating flooding, respectively, with a gas-water ratio of 1:1, a gas injection cycle of 90 days, and a bottom-hole flow pressure of 25 MPa in the production wells. A comparison between the results revealed that the formation pressure and oil recovery efficiency of this well group significantly increased upon CO2 flooding, and the parameter optimization results were well suited for controlling the gas flurry, offering a versatile model for future development of the block.

Mechanism of salt tolerance in the endangered semi-mangrove plant Barringtonia racemosa: anatomical structure and photosynthetic and fluorescence characteristics.

To elucidate the mechanisms governing the salt tolerance of the endangered semi-mangrove plant Barringtonia racemosa, the biomass, photosynthetic and fluorescent characteristics, and anatomical structure of B. racemosa were studied under low, medium and high salt stress. The results showed that the stem dry weight, net photosynthetic rate, intercellular CO2 concentration, Fv/Fm, and ΦPSI of B. racemosa decreased under high salt stress, which led to a significant reduction in total dry weight. Stem dry weight was significantly positively correlated with the thickness of palisade tissue and significantly negatively correlated with the thickness of the epidermis of roots and xylem of stems. Therefore, a stable net photosynthetic rate and intercellular CO2 concentration, an increase in Fv/Fm and ΦPSI, an increase in or stable palisade tissue and spongy mesophyll of leaves and an increase in xylem thickness of the stem and epidermis, outer cortex, and stele diameter of roots could contribute to the salt tolerance of B. racemosa.

PRDX6 alleviated heart failure by inhibiting doxorubicin-induced ferroptosis through the JAK2/STAT1 pathway inactivation.

Peroxiredoxin 6 (PRDX6) is a protective biomarker associated with ferroptosis in heart failure (HF). This study investigated the specific mechanism of PRDX6 on doxorubicin (DOX)-induced ferroptosis in HF. Wistar rats and H9c2 cells were induced by DOX to construct HF models. Pathological changes and collagen deposition in myocardium were investigated using HE and Masson staining. PRDX6 levels, indexes of ferroptosis, and JAK2/STAT1 pathway were detected by qRT-PCR, Western blot, and biochemical kits. DOX promoted heart weight/body weight, increased inflammation and collagen deposition, increased PTGS2 and MDA levels, and decreased SLC7A11, GPX4, FTH1, and PRDX6 levels in myocardium. PRDX6 overexpression reduced PTGS2, MDA, Fe2+, and LDH levels, inhibited JAK2 and STAT1 phosphorylation, and increased SLC7A11, GPX4, and FTH1 levels in DOX-added H9c2 cells. RO8191 and erastin reversed the inhibition of PRDX6 on ferroptosis through the JAK2/STAT1 pathway. Overall, PRDX6 alleviated HF by inhibiting DOX-induced ferroptosis through the JAK2/STAT1 pathway inactivation.

Carbon-reinforced Ni3S2/Ti3C2Tx MXene composite as an anode for superior-performance lithium-ion capacitors.

Lithium ion capacitors (LICs) are a new generation of energy storage devices that combine the super energy storage capability of lithium ion batteries with the satisfactory power density of supercapacitors. The development of high-performance LICs still faces great challenges due to the unbalanced reaction kinetics at the anode and cathode. Therefore, it is an inevitable need to enhance the electron/ion transfer capability of the anode materials. In this paper, to obtain a superior-rate and high-capacity Ni3S2-based anode, highly conductive Ti3C2Tx MXene sheets were introduced to sever as the carrier of Ni3S2 nanoparticles and simultaneously an amorphous carbon layer which coats onto the surface of Ni3S2 nanoparticles was in-situ generated by the carbonization of dopamine reactant. The as-synthesized Ni3S2/Ti3C2Tx/C composite exhibits a high specific surface area (112.6 m2/g) because of the addition of Ti3C2Tx that can reduce the aggregation of Ni3S2 nanoparticles and the in-situ generated amorphous carbon layer that can suppress the growth of Ni3S2 nanoparticles. The Ni3S2/Ti3C2Tx/C anode possesses a remarkable reversible discharge specific capacity (626.0 mAh/g under 0.2 A/g current density), which increases to 1150.8 mAh/g after 400-cycle charge/discharge measurement at the same measurement condition indicating eminent cyclability, along with superior rate capability. To construct a superior-performance LIC device, a sterculiae lychnophorae derived porous carbon (SLPC) cathode with an average discharge specific capacity of 73.4 mAh/g@0.1A/g was prepared. The Ni3S2/Ti3C2Tx/C//SLPC LIC device with optimal cathode/anode mass ratio has a satisfactory energy density ranging from 32.8 to 119.1 Wh kg-1 at the corresponding power density of 8799.4 to 157.5 W kg-1, together with a prominent capacity retention (95.5 %@1 A/g after 10,000 cycles).

A CRISPR/LbCas12a-based method for detection of bacterial fruit blotch pathogens in watermelon.

Acidovorax citrulli is the main pathogen causing bacterial fruit blotch, which seriously threatens the global watermelon industry. At present, rapid, sensitive, and low-cost detection methods are urgently needed. The established CRISPR/LbCas12a visual detection method can specifically detect A. citrulli and does not cross-react with other pathogenic bacteria such as Erwinia tracheiphila, Pseudomonas syringae, and Xanthomonas campestris. The sensitivity of this method for genomic DNA detection is as low as 0.7 copies/µL, which is higher than conventional PCR and real-time PCR. In addition, this method only takes 2.5 h from DNA extraction to quantitative detection and does not require complex operation and sample treatment. Additionally, the technique was applied to test real watermelon seed samples for A. citrulli, and the results were contrasted with those of real-time fluorescence quantitative PCR and conventional PCR. The high sensitivity and specificity have broad application prospects in the rapid detection of bacterial fruit blotch bacterial pathogens of watermelon.IMPORTANCEBacterial fruit blotch, Acidovorax citrulli, is an important seed-borne bacterial disease of watermelon, melon, and other cucurbits. The lack of rapid, sensitive, and reliable pathogen detection methods has hampered research on fruit spot disease prevention and control. Here, we demonstrate the CRISPR/Cas12a system to analyze aspects of the specificity and sensitivity of A. citrulli and to test actual watermelon seed samples. The results showed that the CRISPR/Cas12a-based free-amplification method for detecting bacterial fruit blotch pathogens of watermelons was specific for A. citrulli target genes and 100-fold more sensitive than conventional PCR with quantitative real-time PCR. This method provides a new technical tool for the detection of A. citrulli.

3D Printing Architecting ß-PVDF Reservoirs for Preferential ZnO Epitaxial Growth Toward Advanced Piezoelectric Energy Harvesting.

For polyvinylidene fluoride (PVDF) based piezoelectric composites, epitaxial growth of ZnO nanorods (ZnO-nr) piezoceramic layer on PVDF is an effective way to improve their piezoelectric performance. However, the crystal nucleus of ZnO featuring polar surfaces that cannot be directly attached to hydrophobic PVDF with low surface energy. Herein, direct ink writing (DIW) 3D printing is employed for the first time to create ß-PVDF reservoirs with significantly enhanced surface energy, facilitating the attachment and epitaxial growth of ZnO-nr. The printed ß-PVDF reservoirs designed with programmed macro-pores and abundant inner micropores, enable a higher loading of ZnO-nr by more than one magnitude, thereby boosting the electro-mechanical response. The resulting PVDF/ZnO core-shell piezoelectric energy harvester (PEH) delivers an output voltage of 33.2 V, as well as an unprecedentedly high relative output voltage of 2.76 V/wt.%, which is 2.63 times that of the state-of-the-art 3D-printed PVDF/piezoceramics PEHs. Furthermore, it can differentiate subtle human motions whereas hybrid PEHs cannot distinct. This work demonstrates that the DIW 3D printing approach offers a simple and convenient design idea for creating high performance PEHs.

Exploring negative emission potential of biochar to achieve carbon neutrality goal in China.

Limiting global warming to within 1.5 °C might require large-scale deployment of premature negative emission technologies with potentially adverse effects on the key sustainable development goals. Biochar has been proposed as an established technology for carbon sequestration with co-benefits in terms of soil quality and crop yield. However, the considerable uncertainties that exist in the potential, cost, and deployment strategies of biochar systems at national level prevent its deployment in China. Here, we conduct a spatially explicit analysis to investigate the negative emission potential, economics, and priority deployment sites of biochar derived from multiple feedstocks in China. Results show that biochar has negative emission potential of up to 0.92 billion tons of CO2 per year with an average net cost of US$90 per ton of CO2 in a sustainable manner, which could satisfy the negative emission demands in most mitigation scenarios compatible with China's target of carbon neutrality by 2060.

Superhydrophobic Surface-Assisted Preparation of Microspheres and Supraparticles and Their Applications.

Superhydrophobic surface (SHS) has been well developed, as SHS renders the property of minimizing the water/solid contact interface. Water droplets deposited onto SHS with contact angles exceeding 150°, allow them to retain spherical shapes, and the low adhesion of SHS facilitates easy droplet collection when tilting the substrate. These characteristics make SHS suitable for a wide range of applications. One particularly promising application is the fabrication of microsphere and supraparticle materials. SHS offers a distinct advantage as a universal platform capable of providing customized services for a variety of microspheres and supraparticles. In this review, an overview of the strategies for fabricating microspheres and supraparticles with the aid of SHS, including cross-linking process, polymer melting, and droplet template evaporation methods, is first presented. Then, the applications of microspheres and supraparticles formed onto SHS are discussed in detail, for example, fabricating photonic devices with controllable structures and tunable structural colors, acting as catalysts with emerging or synergetic properties, being integrated into the biomedical field to construct the devices with different medicinal purposes, being utilized for inducing protein crystallization and detecting trace amounts of analytes. Finally, the perspective on future developments involved with this research field is given, along with some obstacles and opportunities.

Ivermectin induces nonprotective autophagy by downregulating PAK1 and apoptosis in lung adenocarcinoma cells.

INTRODUCTION: LUAD (Lung adenocarcinoma), the most common subtype of lung carcinoma and one of the highest incidences and mortality cancers in the world remains still a substantial treatment challenge. Ivermectin, an avermectin derivative, has been traditionally used as an antiparasitic agent in human and veterinary medicine practice during the last few decades. Though ivermectin has been shown to be effective against a variety of cancers, however, there is few available data reporting the antitumor effects of ivermectin in LUAD. METHODS: The effect of ivermectin on cell viability and proliferative ability of LUAD cells was evaluated using CCK-8 and colony formation assay. Apoptosis rate and autophagy flux were detected using flow cytometry based on PI/Annexin V staining and confocal laser scanning microscope based on LC3-GFP/RFP puncta, respectively. Western blotting experiment was conducted to verify the results of changes in apoptosis and autophagy. LUAD-TCGA and GEO databases were used to analyse the expression and predictive value of PAK1 in LUAD patients. Xenograft model and immumohistochemical staining were used for verification of the inhibitor effect of ivermectin in vivo. RESULTS: Ivermectin treatment strikingly impeded the colony formation, and the viability of the cell, along with cell proliferation, and caused the apoptosis and enhanced autophagy flux in LUAD cells. In addition, ivermectin-induced nonprotective autophagy was confirmed by treating LUAD cells with 3-MA, an autophagy inhibitor. Mechanistically, we found that ivermectin inhibited PAK1 protein expression in LUAD cells and we confirmed that overexpression of PAK1 substantially inhibited ivermectin-induced autophagy in LUAD cells. Based on TCGA and GEO databases, PAK1 was highly expressed in LUAD tissues as compared with normal tissues. Furthermore, LUAD patients with high PAK1 level have poor overall survival. Finally, in vivo experiments revealed that ivermectin efficiently suppressed the cellular growth of LUAD among nude mice. CONCLUSION: This study not only revealed the mechanism of ivermectin inhibited the growth of LUAD but also supported an important theoretical basis for the development of ivermectin during the therapy for LUAD.

Targeting epidermal growth factor receptor signalling pathway: A promising therapeutic option for COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously producing new variants, necessitating effective therapeutics. Patients are not only confronted by the immediate symptoms of infection but also by the long-term health issues linked to long COVID-19. Activation of epidermal growth factor receptor (EGFR) signalling during SARS-CoV-2 infection promotes virus propagation, mucus hyperproduction, and pulmonary fibrosis, and suppresses the host's antiviral response. Over the long term, EGFR activation in COVID-19, particularly in COVID-19-induced pulmonary fibrosis, may be linked to the development of lung cancer. In this review, we have summarised the significance of EGFR signalling in the context of SARS-CoV-2 infection. We also discussed the targeting of EGFR signalling as a promising strategy for COVID-19 treatment and highlighted erlotinib as a superior option among EGFR inhibitors. Erlotinib effectively blocks EGFR and AAK1, thereby preventing SARS-CoV-2 replication, reducing mucus hyperproduction, TNF-α expression, and enhancing the host's antiviral response. Nevertheless, to evaluate the antiviral efficacy of erlotinib, relevant clinical trials involving an appropriate patient population should be designed.

Anti-Environmental Aging Passive Daytime Radiative Cooling.

Passive daytime radiative cooling technology presents a sustainable solution for combating global warming and accompanying extreme weather, with great potential for diverse applications. The key characteristics of this cooling technology are the ability to reflect most sunlight and radiate heat through the atmospheric transparency window. However, the required high solar reflectance is easily affected by environmental aging, rendering the cooling ineffective. In recent years, significant advancements have been made in understanding the failure mechanisms, design strategies, and manufacturing technologies of daytime radiative cooling. Herein, a critical review on anti-environmental aging passive daytime radiative cooling with the goal of advancing their commercial applications is presented. It is first introduced the optical mechanisms and optimization principles of radiative cooling, which serve as a basis for further endowing environmental durability. Then the environmental aging conditions of passive daytime radiative cooling, mainly focusing on UV exposure, thermal aging, surface contamination and chemical corrosion are discussed. Furthermore, the developments of anti-environmental aging passive daytime radiative cooling materials, including design strategies, fabrication techniques, structures, and performances, are reviewed and classified for the first time. Last but not the least, the remaining open challenges and the insights are presented for the further promotion of the commercialization progress.

Up-regulation of miR-155 protects against chronic heart failure by inhibiting HIF-1α.

BACKGROUND: Despite a crucial role of miR-155 in human cancers, its function in heart failure (HF) is still under investigation. This study was designed to explore its association with HF. METHODS: The abdominal transverse aortic constriction (TAC) was adopted for establishment of mouse HF models. qRT-PCR and WB were adopted to detect the changes of miR-155, HIF-1α, Cle-caspase-3, BCL2 and Bax levels in myocardial cells and heart tissues. The changes of cardiac function were checked by ultrasound. Additionally, luciferase reporter gene was adopted for interaction analysis of miR-155 with HIF-1α, and in situ end labelling method was used for detecting myocardial apoptosis. RESULTS: MiR-155 in myocardial tissue of HF mice was significantly down regulated. In HF mice injected with agomiR-155, the up-regulation of miR-155 strongly improved cardiac function, and also significantly lowered the protein levels of apoptosis-associated markers, C-caspase-3 and Bax, but up regulated Bcl-2. Additionally, HIF-1α was identified as the direct target of miR-155. As expected, over-expression of HIF-1α greatly reversed the effects of agomiR-155 on cardiac function and the expression of apoptosis-associated markers in heart tissues of HF mice. CONCLUSION: MiR-155 overexpression can suppress myocardial cell apoptosis through HIF-1α, and strongly alleviate the cardiac function damage in HF mice, indicating the potential of miR-155/HIF-1α axis to be a target for the diagnosis and therapy of HF.

Not in black or white, encryption of grayscale images by donor-acceptor Stenhouse adducts.

Invisible inks have been applied for the secrecy of texts, symbols and binary images. Based on the photochromism of donor-acceptor Stenhouse adducts (DASAs) in the solid-state promoted by ester-containing molecules, we report the encryption of grayscale information by controlling the kinetics of photoisomerization.

Ultra-durable superhydrophobic cellular coatings.

Developing versatile, scalable, and durable coatings that resist the accretion of matters (liquid, vapor, and solid phases) in various operating environments is important to industrial applications, yet has proven challenging. Here, we report a cellular coating that imparts liquid-repellence, vapor-imperviousness, and solid-shedding capabilities without the need for complicated structures and fabrication processes. The key lies in designing basic cells consisting of rigid microshells and releasable nanoseeds, which together serve as a rigid shield and a bridge that chemically bonds with matrix and substrate. The durability and strong resistance to accretion of different matters of our cellular coating are evidenced by strong anti-abrasion, enhanced anti-corrosion against saltwater over 1000 h, and maintaining dry in complicated phase change conditions. The cells can be impregnated into diverse matrixes for facile mass production through scalable spraying. Our strategy provides a generic design blueprint for engineering ultra-durable coatings for a wide range of applications.

Rapid access to icetexane diterpenes: Their protective effects against lipopolysaccharides-induced acute lung injury via PI3K/AKT/NF-κB axis in macrophages.

Acute lung injury (ALI) is a life-threatening disease with limited therapeutic options available in clinic. Development of novel strategies and drugs for anti-ALI therapy are urgently needed. In this study, a facile synthesis of 21 icetexane diterpenes and derivatives with widely-varied oxidation states, particularly the taxamairins that are otherwise challenging to access, were developed from the readily available carnosic acid. Further explorations of their biological implications led to the identification of taxamairin B (6) as a potent anti-inflammatory agent by decreasing the gene expressions of proinflammatory cytokines (TNF-α, IL-1ß and IL-6), as well as mitigating NO and ROS production, within LPS-induced RAW264.7 cells. Taxamairin B (6, 25 mg/kg) also exerted significant protective effects against in LPS-induced ALI in mice. Mechanistic insights drawn from the transcriptomic analysis revealed that taxamairin B (6) down-regulated the PI3K-AKT pathway, along with the suppression of the nuclear translocation of NF-κB. This study not only paves a new pathway to taxamairins, but also provides novel drug leads for the development of anti-inflammatory agents with unique mode of actions.

A standing Leidenfrost drop with Sufi whirling.

When a water drop is placed on a hot solid surface, it either undergoes explosive contact boiling or exhibits a stable state. In the latter case, the drop floats over an insulating layer of vapor generated by rapid vaporization of water at the surface/drop interface; this is known as the Leidenfrost state. Here, we discuss a previously unrecognized steady state in which a water drop "stands" on a hot smooth surface. In this state, the drop stabilizes itself with partial adhesion on the hot surface, leading to unique deformation and rotation behavior reminiscent of Sufi whirling-a form of spinning dance. Our analysis of this standing Leidenfrost state reveals the underlying mechanisms that drive the drop's stable partial adhesion and subsequent deformation with rotation. The heat-transfer efficiency of this standing state is up to 390% greater than that of the traditional floating Leidenfrost state.