Imperceptible augmentation of living systems with organic bioelectronic fibres.

The functional and sensory augmentation of living structures, such as human skin and plant epidermis, with electronics can be used to create platforms for health management and environmental monitoring. Ideally, such bioelectronic interfaces should not obstruct the inherent sensations and physiological changes of their hosts. The full life cycle of the interfaces should also be designed to minimize their environmental footprint. Here we report imperceptible augmentation of living systems through in situ tethering of organic bioelectronic fibres. Using an orbital spinning technique, substrate-free and open fibre networks-which are based on poly (3,4-ethylenedioxythiophene):polystyrene sulfonate-can be tethered to biological surfaces, including fingertips, chick embryos and plants. We use customizable fibre networks to create on-skin electrodes that can record electrocardiogram and electromyography signals, skin-gated organic electrochemical transistors and augmented touch and plant interfaces. We also show that the fibres can be used to couple prefabricated microelectronics and electronic textiles, and that the fibres can be repaired, upgraded and recycled.

Razor clam (Pinna bicolor) structural mimics as drivers of epibenthic biodiversity; a manipulative experiment.

Shellfish ecosystems facilitate important ecological functions and communities, but overexploitation and mismanagement have contributed to their decline worldwide. Within recent decades, coastal management efforts have increasingly sought to understand and reinstate valuable ecological functions provided by habitat-forming bivalves including oysters, mussels and pinnids. However, many bivalve species are critically understudied, limiting restoration and ecological engineering opportunities. Pinnids, specifically, are an underappreciated bivalve group, with razor clams (Pinna bicolor) forming dense aggregations, and potentially supporting important ecological functions. This study, conducted in an urban Australian estuary, was a manipulative experiment that investigated whether artificial razor clam shells could facilitate beneficial ecological functions through the provision of structural habitat. Specifically, we investigated the influence of intertidal benthic structures, including the micro-habitat influences of surface structure associated with mortality status (open or closed shell), and the short-term response of the benthic and epifaunal communities. Within 12 weeks, the structural razor clam mimics rapidly changed the aboveground ecological community, relative to the bare habitat controls. Both open and closed artificial shells provided a settlement surface for epiphytic organisms and supported enhanced epifaunal biodiversity. Contrastingly, the artificial structures did not significantly alter sediment characteristics or infaunal macroinvertebrate composition in the surrounding benthos. These results provide important insights into the rapid ecological response to the installation of intertidal pinnid structures in dynamic estuarine ecosystems. Furthermore, we provide a case study for understanding the ecological functions of an understudied habitat-forming species, which could be used to inform future restoration and management efforts.

Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing.

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

Magnesium-promoted rapid self-reconstruction of NiFe-based electrocatalysts toward efficient oxygen evolution.

The acceleration of active sites formation through surface reconstruction is widely acknowledged as the crucial factor in developing high-performance oxygen evolution reaction (OER) catalysts for water splitting. Herein, a simple one-step corrosion method and magnesium (Mg)-promoted strategy are reported to develop the NiFe-based catalyst with enhanced OER performance. The Mg is introduced in NiFe materials to preparate a "pre-catalyst" Mg-Ni/Fe2O3. In-situ Raman shows that Mg doping would accelerate the self-reconstruction of Ni/Fe2O3 to form active NiOOH species during OER. In-situ infrared indicates that Mg doping benefits the formation of *OOH intermediate. Theoretical analysis further confirms that Mg doping can optimize the adsorption of oxygen intermediates, accelerating the OER kinetics. Accordingly, the Mg-Ni/Fe2O3 catalyst exhibits excellent OER performance with overpotential of 168 mV at 10 mA cm-2. The anion exchange membrane water electrolyzer achieved 200 mA cm-2 at voltage of 1.53 V, showing excellent stability over 500 h as well. This work demonstrates the potential of Mg-promoted strategy in regulating the activity of transition metal-based OER electrocatalysts.

Bivalent target-binding bioPROTACs induce potent degradation of oncogenic SHP2.

Targeted protein degradation is an emergent and rapidly evolving therapeutic strategy. In particular, biologics-based targeted degradation modalities (bioPROTACs) are relatively under explored compared to small molecules. Here, we investigate how target affinity, cellular localization, and valency of bioPROTACs impact efficacy of targeted degradation of the oncogenic phosphatase src-homology 2 containing protein tyrosine phosphatase-2 (SHP2). We identify bivalent recruitment of SHP2 by bioPROTACs as a broadly applicable strategy to improve potency. Moreover, we demonstrate that SHP2-targeted bioPROTACs can effectively counteract gain-of-function SHP2 mutants present in cancer, which are otherwise challenging to selectively target with small molecule constructs. Overall, this study demonstrates the utility of bioPROTACs for challenging targets, and further explicates design principles for therapeutic bioPROTACs.

Evaluating the feasibility of medium chain oleochemical synthesis using microbial chain elongation.

Chain elongating bacteria are a unique guild of strictly anaerobic bacteria that have garnered interest for sustainable chemical manufacturing from carbon-rich wet and gaseous waste streams. They produce C6-C8 medium-chain fatty acids which are valuable platform chemicals that can be used directly, or derivatized to service a wide range of chemical industries. However, the application of chain elongating bacteria for synthesizing products beyond C6-C8 medium-chain fatty acids has not been evaluated. In this study, we assess the feasibility of expanding the product spectrum of chain elongating bacteria to C9-C12 fatty acids, along with the synthesis of C6 fatty alcohols, dicarboxylic acids, diols, and methyl ketones. We propose several metabolic engineering strategies to accomplish these conversions in chain elongating bacteria and utilize constraint-based metabolic modelling to predict pathway stoichiometries, assess thermodynamic feasibility, and estimate ATP and product yields. We also evaluate how producing alternative products impacts the growth rate of chain elongating bacteria via resource allocation modelling, revealing a trade-off between product carbon length and class versus cell growth rate. Together, these results highlight the potential for using chain elongating bacteria as a platform for diverse oleochemical biomanufacturing and offer a starting point for guiding future metabolic engineering efforts aimed at expanding their product range.

Rational design of disulfide bonds to increase thermostability of Rhodococcus opacus catechol 1,2 dioxygenase.

Catechol 1,2 dioxygenase is a versatile enzyme with several potential applications. However, due to its low thermostability, its industrial potential is not being met. In this study, the thermostability of a mesophilic catechol 1,2 dioxygenase from the species Rhodococcus opacus was enhanced via the introduction of disulphide bonds into its structure. Engineered designs (56) were obtained using computational prediction applications, with a set of hypothesized selection criteria narrowing the list to 9. Following recombinant production and purification, several of the designs demonstrated substantially improved protein thermostability. Notably, variant K96C-D278C yielded improvements including a 4.6°C increase in T50, a 725% increase in half-life, a 5.5°C increase in Tm, and a >10-fold increase in total turnover number compared to wild type. Stacking of best designs was not productive. Overall, current state-of-the-art prediction algorithms were effective for design of disulfide-thermostabilized catechol 1,2 dioxygenase.

Three-in-One: Molecular Engineering of D-A-π-A Featured Type I and Type II Near-Infrared AIE Photosensitizers for Efficient Photodynamic Cancer Therapy and Bacteria Killing.

Bacterial infections are closely correlated with the genesis and progression of cancer, and the elimination of cancer-related bacteria may improve the efficacy of cancer treatment. However, the combinatorial therapy that utilizes two or more chemodrugs will increase potential adverse effects. Image-guided photodynamic therapy is a highly precise and potential therapy to treat tumor and microbial infections. Herein, four donor-acceptor-π-bridge-acceptor (D-A-π-A) featured near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) (TQTPy, TPQTPy, TQTC, and TPQTC) with type I and type II reaction oxygen species (ROS) generation capabilities are synthesized. Notably, TQTPy shows mitochondria targeted capacity, the best ROS production efficiency, long-term tumor retention capacity, and more importantly, the three-in-one fluorescence imaging guided therapy against both tumor and microbial infections. Both in vitro and in vivo results validate that TQTPy performs well in practical biomedical application in terms of NIR-fluorescence imaging-guided photodynamic cancer diagnosis and treatment. Moreover, the amphiphilic and positively charged TQTPy is able to specific and ultrafast discrimination and elimination of Gram-positive (G+) Staphylococcus aureus from Gram-negative (G-) Escherichia coli and normal cells. This investigation provides an instructive way for the construction of three-in-one treatment for image-guided photodynamic cancer therapy and bacteria elimination.

Zinc phosphate glass microspheres promoted mineralization and expression of BMP2 in MC3T3-E1 cells.

Degradable phosphate glasses have shown favorable properties for tissue engineering. By changing the composition of the glasses, the degradation rate, and ion release are controllable. Zinc oxide can function as a glass network modifier and has been shown to play a positive role in bone formation. Also, phosphate glasses can easily be processed into microspheres, which can be used as microcarriers. This study aims to develop zinc phosphate glasses microspheres and explore the optimized size and composition for applications in bone tissue engineering. Zinc-titanium-calcium-sodium phosphate glasses with 0, 1, 3, 5, or 10 mol % zinc oxide were prepared and processed into microspheres. The smaller microspheres ranged in size from 50 to 106 µm, while the larger ones ranged from 106 to 150 µm. The characteristics of glasses were examined. The osteoblastic cell line MC3T3-E1 was cultured on the surface of microspheres and the cell viability was examined. To evaluate osteogenic differentiation, Alizarin Red S staining, quantitative reverse transcription polymerase chain reaction, and western blot analysis were performed after 14 days. Different sizes of zinc phosphate glass microspheres were successfully made. The glass microspheres with <10 mol % zinc oxide were able to support the adhesion and proliferation of MC3T3-E1 cell lines. The relative gene expression of BMP2 was significantly upregulated in the smaller glass microspheres containing 3 mol % zinc oxide (26-fold, p < .001) and both sizes of microspheres containing 5 mol % zinc oxide (smaller: 27-fold, p < .001; larger: 35-fold, p < .001). Additionally, cluster formation was observed in glass microspheres after 14 days, and the mineralization of MC3T3-E1 cell lines was promoted. Based on these findings, the glass microspheres containing 3-5 mol % of zinc oxide can promote osteogenic differentiation for MC3T3-E1 cells.

Does Scaling Up Pig Farming Promote Carbon Neutrality Among Pig Farmers?

Pig farming is a major source of carbon emissions in China's livestock industry, and the promotion and application of carbon neutral technologies dedicated to carbon reduction and sequestration is a key measure to promote the realization of carbon neutrality in pig farming industry. In the absence of a system for carbon emission reduction in agriculture, it is important to explore whether large-scale pig farming can spontaneously promote the application of carbon neutral technologies by pig farmers. Combined with the technical background of carbon neutrality in pig farming industry and using the field survey data of 468 pig farmers in Shandong Province, this paper empirically analyzed the effect of large-scale pig farming on the carbon neutral behavior of pig farmers. The findings are threefold. Firstly, because of the effect of economies of scale in the application of carbon neutral technologies, large-scale pig farming can promote the carbon neutral behavior of pig farmers. However, the effect of economies of scale in the application of carbon neutral technologies has a boundary, and the annual output of pigs should be maintained at 3000 to 4999. Secondly, among the effects of pig breeding scale on the application and its degree of composting project, state of planting and breeding cycle has no regulating effect. Thirdly, among the effects of pig breeding scale on the application and its degree of biogas engineering, both state of planting and breeding cycle and subsidy for construction of biogas digester have negative regulating effects. In this paper, the pig farming industry is taken as a typical example to reveal the endogenous incentive mechanism of promoting agricultural carbon emission reduction, which provides theoretical reference and experience enlightenment for the formulation of effective policies to promote agricultural carbon neutrality, which are different from industrial industries.

Impact of cardiac patch alignment on restoring post-infarct ventricular function.

Acute myocardial infarction (MI) leads to a loss of cardiac function which, following adverse ventricular remodeling (AVR), can ultimately result in heart failure. Tissue-engineered contractile patches placed over the infarct offer potential for restoring cardiac function and reducing AVR. In this computational study, we investigate how improvement of pump function depends on the orientation of the cardiac patch and the fibers therein relative to the left ventricle (LV). Additionally, we examine how model outcome depends on the choice of material properties for healthy and infarct tissue. In a finite element model of LV mechanics, an infarction was induced by eliminating active stress generation and increasing passive tissue stiffness in a region comprising 15% of the LV wall volume. The cardiac patch was modeled as a rectangular piece of healthy myocardium with a volume of 25% of the infarcted tissue. The orientation of the patch was varied from 0 to 150 ∘ relative to the circumferential plane. The infarct reduced stroke work by 34% compared to the healthy heart. Optimal patch support was achieved when the patch was oriented parallel to the subepicardial fiber direction, restoring 9% of lost functionality. Typically, about one-third of the total recovery was attributed to the patch, while the remainder resulted from restored functionality in native myocardium adjacent to the infarct. The patch contributes to cardiac function through two mechanisms. A contribution of tissue in the patch and an increased contribution of native tissue, due to favorable changes in mechanical boundary conditions.

Microfluidic chips in female reproduction: a systematic review of status, advances, and challenges.

The female reproductive system is essential to women's health, human reproduction and societal well-being. However, the clinical translation of traditional research models is restricted due to the uncertain effects and low efficiency. Emerging evidence shows that microfluidic chips provide valuable platforms for studying the female reproductive system, while no paper has ever comprehensively discussed the topic. Here, a total of 161 studies out of 14,669 records are identified in PubMed, Scopus, Web of Science, ScienceDirect and IEEE Xplore databases. Among these, 61 studies focus on oocytes, which further involves culture, cell surgeries (oocyte separation, rotation, enucleation, and denudation), evaluation and cryopreservation. Forty studies investigate embryo manipulation via microfluidic chips, covering in vitro fertilization, cryopreservation and functional evaluation. Forty-six studies reconstitute both the physiological and pathological statuses of in vivo organs, mostly involved in placenta and fetal membrane research. Fourteen studies perform drug screening and toxicity testing. In this review, we summarize the current application of microfluidic chips in studying the female reproductive system, the advancements in materials and methods, and discuss the future challenges. The present evidence suggests that microfluidic chips-assisted reproductive system reconstruction is promising and more studies are urgently needed.

Harnessing LLMs for multi-dimensional writing assessment: Reliability and alignment with human judgments.

Recent advancements in natural language processing, computational linguistics, and Artificial Intelligence (AI) have propelled the use of Large Language Models (LLMs) in Automated Essay Scoring (AES), offering efficient and unbiased writing assessment. This study assesses the reliability of LLMs in AES tasks, focusing on scoring consistency and alignment with human raters. We explore the impact of prompt engineering, temperature settings, and multi-level rating dimensions on the scoring performance of LLMs. Results indicate that prompt engineering significantly affects the reliability of LLMs, with GPT-4 showing marked improvement over GPT-3.5 and Claude 2, achieving 112% and 114% increase in scoring accuracy under the criteria and sample-referenced justification prompt. Temperature settings also influence the output consistency of LLMs, with lower temperatures producing scores more in line with human evaluations, which is essential for maintaining fairness in large-scale assessment. Regarding multi-dimensional writing assessment, results indicate that GPT-4 performs well in dimensions regarding Ideas (QWK=0.551) and Organization (QWK=0.584) under well-crafted prompt engineering. These findings pave the way for a comprehensive exploration of LLMs' broader educational implications, offering insights into their capability to refine and potentially transform writing instruction, assessment, and the delivery of diagnostic and personalized feedback in the AI-powered educational age. While this study attached importance to the reliability and alignment of LLM-powered multi-dimensional AES, future research should broaden its scope to encompass diverse writing genres and a more extensive sample from varied backgrounds.

Strategies for overcoming challenges in selective electrochemical CO2 conversion to ethanol.

The electrochemical conversion of carbon dioxide (CO2) to valuable chemicals is gaining significant attention as a pragmatic solution for achieving carbon neutrality and storing renewable energy in a usable form. Recent research increasingly focuses on designing electrocatalysts that specifically convert CO2 into ethanol, a desirable product due to its high-energy density, ease of storage, and portability. However, achieving high-efficiency ethanol production remains a challenge compared to ethylene (a competing product with a similar electron configuration). Existing electrocatalytic systems often suffer from limitations such as low energy efficiency, poor stability, and inadequate selectivity toward ethanol. Inspired by recent progress in the field, this review explores fundamental principles and material advancements in CO2 electroreduction, emphasizing strategies for ethanol production over ethylene. We discuss electrocatalyst design, reaction mechanisms, challenges, and future research directions. These advancements aim to bridge the gap between current research and industrialized applications of this technology.

Capillary effect-based selective sealing strategy for increasing piezoelectric MEMS speaker performance.

To address the serious acoustic performance deterioration induced by air leakage in the low-frequency range and the asynchronous vibration in electroacoustic transduction structures near the resonant frequency, a novel sealing strategy is proposed that targets one of the most widely reported piezoelectric MEMS speaker designs. This design consists of multiple cantilever beams, in which the air gaps between cantilevers are automatically and selectively filled with liquid polydimethylsiloxane (PDMS) via the capillary effect, followed by curing. In the proof-of-concept demonstration, the sound pressure level (SPL) within the frequency range lower than 100 Hz markedly increased after sealing in an experiment using an IEC ear simulator. Specifically, the SPL is increased by 4.9 dB at 20 Hz for a 40 Vpp driving voltage. Moreover, the deteriorated SPL response near the resonant frequencies of the cantilever beams (18 kHz-19 kHz) caused by their asynchronous vibration induced by the fabrication process nonuniformity also significantly improved, which successfully increased the SPL to approximately 17.5 dB. Moreover, sealed devices feature nearly the same SPL response as the initial counterpart in the frequency band from 100 Hz to 16 kHz and a total harmonic distortion (THD) of 0.728% at 1 kHz for a 40 Vpp driving voltage. Compared with existing sealing methods, the current approach offers easy operation, low damage risk, excellent repeatability/reliability and excellent robustness advantages and provides a promising technical solution for MEMS acoustic devices.

Evolutionary Design of Self-Templated Supramolecular Fibrils Using M13 Bacteriophage for Tissue Engineering.

Biomaterials in nature form hierarchical structures and functions across various length scales through binding and assembly processes. Inspired by nature, we developed hierarchically organized tissue engineering materials through evolutionary screening and self-templating assembly. Leveraging the M13 bacteriophage (phage), we employed an evolutionary selection process against hydroxyapatite (HA) to isolate HA-binding phage (HAPh). The newly discovered phage exhibits a bimodal length, comprising 950 nm and 240 nm, where the synergistic effect of these dual lengths promotes the formation of supramolecular fibrils with periodic banded structures. The assembled HAPh fibrils show the capability of HA mineralization and the directional growth of osteoblast cells. When applied to a dentin surface, it induces the regeneration of dentin-like tissue structures, showcasing its potential applications as a scaffold in tissue engineering. The integration of evolutionary screening and self-templating assembly holds promise for the future development of hierarchically organized tissue engineering materials.

Heterologous Expression of Epoxomicin in Escherichia coli.

Epoxomicin is an epoxyketone proteasome inhibitor with synthetic derivatives approved or under investigation for treatment of multiple myeloma. To leverage the advantages of Escherichia coli as a rapidly growing and readily engineered host for the production of epoxomicin and analogues, we expressed codon-optimized versions of the epoxomicin biosynthetic genes, epxD, epxE, and epxF. Epoxomicin was detected, but the major product was a ketone resulting from α,ß-keto acid precursor decarboxylation. Epoxomicin yield was improved by altering the copy numbers of each gene and creating a fusion of epxE and epxF. Our optimized system offers promise for efficient engineering and biosynthesis of improved epoxomicin analogues.

An Engineered Imine Reductase for Highly Diastereo- and Enantioselective Synthesis of ß-Branched Amines with Contiguous Stereocenters.

ß-Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo- and enantioselective biocatalytic approach for preparing a broad range of ß-branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution-asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild-type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9% ee, >99:1 dr, and >99% conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74% yield, >99.9% ee, and 98:2 dr at a challenging substrate loading of 110 g L-1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution-asymmetric reductive amination reaction system.

Truncation of a novel C-terminal domain of a ß-glucanase improves its thermal stability and specific activity.

Enzymes that degrade ß-glucan play important roles in various industries, including those related to brewing, animal feed, and health care. Csph16A, an endo-ß-1,3(4)-glucanase encoded by a gene from the halotolerant, xerotolerant, and radiotrophic black fungus Cladosporium sphaerospermum, was cloned and expressed in Pichia pastoris. Two isoforms (Csph16A.1 and Csph16A.2) are produced, arising from differential glycosylation. The proteins were predicted to contain a catalytic Lam16A domain, along with a C-terminal domain (CTD) of unknown function which exhibits minimal secondary structure. Employing PCR-mediated gene truncation, the CTD of Csph16A was excised to assess its functional impact on the enzyme and determine potential alterations in biotechnologically relevant characteristics. The truncated mutant, Csph16A-ΔC, exhibited significantly enhanced thermal stability at 50°C, with D-values 14.8 and 23.5 times greater than those of Csph16A.1 and Csph16A.2, respectively. Moreover, Csph16A-ΔC demonstrated a 20%-25% increase in halotolerance at 1.25 and 1.5 M NaCl, respectively, compared to the full-length enzymes. Notably, specific activity against cereal ß-glucan, lichenan, and curdlan was increased by up to 238%. This study represents the first characterization of a glucanase from the stress-tolerant fungus C. sphaerospermum and the first report of a halotolerant and engineered endo-ß-1,3(4)-glucanase. Additionally, it sheds light on a group of endo-ß-1,3(4)-glucanases from Antarctic rock-inhabiting black fungi harboring a Lam16A catalytic domain and a novel CTD of unknown function.