The impact of bacillus pumilus TS2 isolated from yaks on growth performance, gut microbial community, antioxidant activity, and cytokines related to immunity and inflammation in broilers.

Intensive poultry farming faces challenges like gut inflammation in the absence of antibiotics, resulting in reduced productivity, heightened susceptibility to enteric diseases, and other complications. Alternative strategies are needed to manage inflammation and maintain sustainable poultry production. Yaks living in high-altitude hypoxic environments have specialized gut microbes. However, yak probiotics remain largely uncharacterized. We previously isolated a strain of Bacillus pumilus (named TS2) from yaks and demonstrated its potential as a probiotic in vitro. Therefore, in this study, we evaluated the in vivo growth-promoting, antioxidant, immune, and anti-inflammatory effects of Bacillus pumilus isolated from yaks in broilers. We demonstrated the safety of TS2 isolated from yaks in broilers. Furthermore, we found that TS2 increased the average daily weight gain (ADWG) and reduced the feed conversion ratio (FCR). Supplementation with TS2 also improved the mucosal morphology, the ratio of villi to crypt cells, and enzyme activity. High-throughput sequencing showed that the abundance of Lactobacillus was higher in the TS2 treated broilers. Importantly, the serum level of malondialdehyde (MDA) was reduced and the levels of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were increased in the low-dose TS2 group, while the inflammatory factors interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were downregulated compared with the control group. We demonstrated that TS2 supplementation can increase the overall growth performance and ameliorate the blood parameters related to inflammation and immunity in broilers.

The Potential of Natural Carotenoids-Containing Sericin of the Domestic Silkworm Bombyx mori.

Sericin derived from the white cocoon of Bombyx mori has been attracting more attention for its utilization in food, cosmetics, and biomedicine. The potential health benefits of natural carotenoids for humans have also been well-established. Some rare strains of Bombyx mori (B. mori) produce yellow-red cocoons, which endow a potential of natural carotenoid-containing sericin. We hypothesized that natural carotenoid-containing sericin from yellow-red cocoons would exhibit better properties compared with white cocoon sericin. To investigate the physicochemical attributes of natural carotenoid-containing sericin, we bred two silkworm strains from one common ancestor, namely XS7 and XS8, which exhibited different cocoon colors as a result of the inconsistent distribution of lutein and ß-carotene. Compared with white cocoon sericin, the interaction between carotenoids and sericin molecules in carotenoid-containing sericin resulted in a unique fluorescence emission at 530, 564 nm. The incorporation of carotenoids enhanced the antibacterial effect, anti-cancer ability, cytocompatibility, and antioxidant of sericin, suggesting potential wide-ranging applications of natural carotenoid-containing sericin as a biomass material. We also found differences in fluorescence characteristics, antimicrobial effects, anti-cancer ability, and antioxidants between XS7 and XS8 sericin. Our work for the first time suggested a better application potential of natural carotenoid-containing sericin as a biomass material than frequently used white cocoon sericin.

24-h central pressure is a valuable predictor for left ventricular hypertrophy in non-dialysis patients with chronic kidney disease.

The current research on the relationship between 24-h central pressure and 24-h brachial pressure with left ventricular hypertrophy (LVH) is characterised by limited sample size and inconsistent findings. Furthermore, the association has never been explored in chronic kidney disease (CKD). A multicentre, cross-sectional study among non-dialysis patients with CKD was conducted. All participants underwent brachial and central ambulatory blood pressure monitoring using MobilO-Graph PWA, while trained cardiologists performed echocardiography. In this study, 2117 non-dialysis patients with CKD were examined. 24-h central systolic blood pressure with c2 calibration (24-h c2SBP) demonstrated a stronger association with left ventricular mass index and LVH compared with 24-h brachial systolic blood pressure (24-h bSBP) in the univariate and multivariate regression analyses. The multivariate net reclassification index (NRI) analysis revealed that 24-h c2SBP exhibited greater discriminatory power over 24-h bSBP (NRI = 0.310, 95% CI [0.192-0.429], P < 0.001). Applying 130/135 mmHg as the threshold for 24-h bSBP/c2SBP to cross-classify, the patients were divided into concordant normotension (1509 individuals), isolated brachial hypertension (155 individuals), isolated central hypertension (11 individuals), and concordant hypertension (442 individuals). With concordant normotension as the reference, the multivariable-adjusted ORs were 0.954 (95% CI, 0.534-1.640; P = 0.870) for isolated brachial hypertension and 2.585 (95%CI, 1.841-3.633; P < 0.001) for concordant hypertension. Among non-dialysis patients with CKD, 24-h c2SBP exhibits greater efficacy in identifying the presence of LVH compared with 24-h bSBP. The presence of LVH was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension.

Correction: Celery-derived porous carbon materials for superior performance supercapacitors.

[This corrects the article DOI: 10.1039/D1NA00342A.].

Site 1 protease aggravates acute kidney injury by promoting tubular epithelial cell ferroptosis through SIRT3-SOD2-mtROS signaling.

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a common clinical syndrome with high morbidity and mortality. Ferroptosis, a newly discovered form of oxidative cell death, is involved in the pathogenesis of renal I/R injury; however, the underlying mechanism remains to be explored. Here, we reported that site 1 protease (S1P) promotes ischemic kidney injury by regulating ferroptotic cell death of tubular epithelial cells. S1P abundance was measured in hypoxia/reoxygenation (H/R)-treated Boston University mouse proximal tubular (BUMPT) cells and I/R-induced murine kidney tissue. S1P expression in BUMPT cells and kidneys was initially activated by hypoxic stimulation, accompanied by the ferroptotic response. Blocking S1P blunted H/R-induced ferroptotic cell death, which also restored sirtuin 3 (SIRT3) expression and superoxide dismutase 2 (SOD2) activity in BUMPT cells. Next, inhibition of S1P expression restored I/R-suppressed SIRT3 abundance, SOD2 activity and reduced the elevated level of mitochondria reactive oxygen species (mtROS), which attenuated tubular cell ferroptosis and renal I/R injury. In conclusion, S1P promoted renal tubular epithelial cell ferroptosis under I/R status by activating SIRT3-SOD2-mtROS signaling, thereby accelerating kidney injury. Thus, targeting S1P signaling may serve as a promising strategy for I/R kidney injury.

The function of carnosic acid in lipopolysaccharides-induced hepatic and intestinal inflammation in poultry.

Inflammatory processes are often accompanied by oxidative stress and lipid peroxidation, which might lead to cellular and organ damage. Carnosic acid (CA), an active component found in rosemary, exhibits pharmacological properties including antioxidative, anti-inflammatory, and antiviral effects. The aim of this research was to investigate whether CA can mitigate lipopolysaccharide (LPS)-induced oxidative stress and inflammatory responses in poultry and to understand its underlying mechanisms. We administered CA to broiler chickens via oral gavage and treated them with LPS, followed by analysis of the effects of different dosages of CA on body weight, antioxidative capacity, and inflammatory factors. Carnosic acid had no significant impact on the body weight of broiler chickens. However, serum analysis indicated that the middle dose of CA effectively enhanced the antioxidative capacity and reduced levels of oxidative stress and inflammation-related factors. Moreover, in the liver, CA demonstrated the ability to regulate the expression of proteins such as heat shock protein 60 (HSP60), heat shock protein 70 (HSP70), and P38 mitogen-activated protein kinase (P38), suggesting its protective role against liver damage induced by LPS. In the intestinal tract of broiler chickens, CA regulated the expression and localization of proteins including HSP60, HSP70, NFE2 like bZIP transcription factor 2 (Nrf2), and P38, while also influencing the expression of inflammatory markers such as protein tyrosine phosphatase receptor type C (CD45), and connexin (Cx). These findings revealed the potential protective mechanisms of CA in alleviating oxidative stress and inflammatory damage induced by LPS in poultry. Carnosic acid notably enhanced the chickens' antioxidative capacity by modulating the expression of key proteins, thereby reducing oxidative stress and inflammatory response levels. This study provides a deeper comprehension of the protective mechanisms of CA and its potential impact on avian health.

Harnessing aptamers for the biosensing of cell surface glycans - A review.

Cell surface glycans (CSGs) are essential for cell recognition, adhesion, and invasion, and they also serve as disease biomarkers. Traditional CSG recognition using lectins has limitations such as limited specificity, low stability, high cytotoxicity, and multivalent binding. Aptamers, known for their specific binding capacity to target molecules, are increasingly being employed in the biosensing of CSGs. Aptamers offer the advantage of high flexibility, small size, straightforward modification, and monovalent recognition, enabling their integration into the profiling of CSGs on living cells. In this review, we summarize representative examples of aptamer-based CSG biosensing and identify two strategies for harnessing aptamers in CSG detection: direct recognition based on aptamer-CSG binding and indirect recognition through protein localization. These strategies enable the generation of diverse signals including fluorescence, electrochemical, photoacoustic, and electrochemiluminescence signals for CSG detection. The advantages, challenges, and future perspectives of using aptamers for CSG biosensing are also discussed.

(Pro)renin receptor mediates tubular epithelial cell pyroptosis in diabetic kidney disease via DPP4-JNK pathway.

BACKGROUND: (Pro)renin receptor (PRR) is highly expressed in renal tubules, which is involved in physiological and pathological processes. However, the role of PRR, expressed in renal tubular epithelial cells, in diabetic kidney disease (DKD) remain largely unknown. METHODS: In this study, kidney biopsies, urine samples, and public RNA-seq data from DKD patients were used to assess PRR expression and cell pyroptosis in tubular epithelial cells. The regulation of tubular epithelial cell pyroptosis by PRR was investigated by in situ renal injection of adeno-associated virus9 (AAV9)-shRNA into db/db mice, and knockdown or overexpression of PRR in HK-2 cells. To reveal the underlined mechanism, the interaction of PRR with potential binding proteins was explored by using BioGrid database. Furthermore, the direct binding of PRR to dipeptidyl peptidase 4 (DPP4), a pleiotropic serine peptidase which increases blood glucose by degrading incretins under diabetic conditions, was confirmed by co-immunoprecipitation assay and immunostaining. RESULTS: Higher expression of PRR was found in renal tubules and positively correlated with kidney injuries of DKD patients, in parallel with tubular epithelial cells pyroptosis. Knockdown of PRR in kidneys significantly blunted db/db mice to kidney injury by alleviating renal tubular epithelial cells pyroptosis and the resultant interstitial inflammation. Moreover, silencing of PRR blocked high glucose-induced HK-2 pyroptosis, whereas overexpression of PRR enhanced pyroptotic cell death of HK-2 cells. Mechanistically, PRR selectively bound to cysteine-enrich region of C-terminal of DPP4 and augmented the protein abundance of DPP4, leading to the downstream activation of JNK signaling and suppression of SIRT3 signaling and FGFR1 signaling, and then subsequently mediated pyroptotic cell death. CONCLUSIONS: This study identified the significant role of PRR in the pathogenesis of DKD; specifically, PRR promoted tubular epithelial cell pyroptosis via DPP4 mediated signaling, highlighting that PRR could be a promising therapeutic target in DKD.

NMPFamsDB: a database of novel protein families from microbial metagenomes and metatranscriptomes.

The Novel Metagenome Protein Families Database (NMPFamsDB) is a database of metagenome- and metatranscriptome-derived protein families, whose members have no hits to proteins of reference genomes or Pfam domains. Each protein family is accompanied by multiple sequence alignments, Hidden Markov Models, taxonomic information, ecosystem and geolocation metadata, sequence and structure predictions, as well as 3D structure models predicted with AlphaFold2. In its current version, NMPFamsDB hosts over 100 000 protein families, each with at least 100 members. The reported protein families significantly expand (more than double) the number of known protein sequence clusters from reference genomes and reveal new insights into their habitat distribution, origins, functions and taxonomy. We expect NMPFamsDB to be a valuable resource for microbial proteome-wide analyses and for further discovery and characterization of novel functions. NMPFamsDB is publicly available in http://www.nmpfamsdb.org/ or https://bib.fleming.gr/NMPFamsDB.

Facile and Cost-Effective Fabrication of Highly Sensitive, Fast-Response Flexible Humidity Sensors Enabled by Laser-Induced Graphene.

The need to simplify fabrication processes and reduce costs for high-performance humidity sensors is increasingly vital, especially in fields such as healthcare and agriculture. This study introduces a simple and cost-effective approach using laser-induced graphene (LIG) on a polyimide film to create highly sensitive and fast-response flexible humidity sensors. The LIG acts as the electrode, while the porous polyimide between the interdigital LIG electrodes serves as the humidity sensing material, showing changes in electrical conductivity based on the humidity levels. The LIG humidity sensor, an ionic-conduction type, exhibits remarkable sensitivity, with a 28,231-fold increase in current as relative humidity changes from 26.1 to 90.2%. It also boasts of ultrashort response/recovery times (less than 0.5/7 s), providing significant advantages in detecting rapid and subtle humidity variations compared to a commercially available MEMS humidity sensor. We successfully demonstrated the LIG humidity sensor's capabilities in ultrafast breathing monitoring (≈174 times per minute), moisture detection of grains, and detection of sudden water pipe leakage. Due to its straightforward and cost-effective fabrication process, the LIG humidity sensor holds immense practical value for affordable, widespread use across various applications.

Mesenchymal stem cells-derived extracellular vesicles protect against oxidative stress-induced xenogeneic biological root injury via adaptive regulation of the PI3K/Akt/NRF2 pathway.

Xenogeneic extracellular matrices (xECM) for cell support have emerged as a potential strategy for addressing the scarcity of donor matrices for allotransplantation. However, the poor survival rate or failure of xECM-based organ transplantation is due to the negative impacts of high-level oxidative stress and inflammation on seed cell viability and stemness. Herein, we constructed xenogeneic bioengineered tooth roots (bio-roots) and used extracellular vesicles from human adipose-derived mesenchymal stem cells (hASC-EVs) to shield bio-roots from oxidative damage. Pretreatment with hASC-EVs reduced cell apoptosis, reactive oxygen species generation, mitochondrial changes, and DNA damage. Furthermore, hASC-EV treatment improved cell proliferation, antioxidant capacity, and odontogenic and osteogenic differentiation, while significantly suppressing oxidative damage by activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2) nuclear translocation via p62-associated Kelch-like ECH-associated protein 1 (KEAP1) degradation. Inhibition of PI3K/Akt and Nrf2 knockdown reduced antioxidant capacity, indicating that the PI3K/Akt/NRF2 pathway partly mediates these effects. In subcutaneous grafting experiments using Sprague-Dawley rats, hASC-EV administration significantly enhanced the antioxidant effect of the bio-root, improved the regeneration efficiency of periodontal ligament-like tissue, and maximized xenograft function. Conclusively, therefore, hASC-EVs have the potential to be used as an immune modulator and antioxidant for treating oxidative stress-induced bio-root resorption and degradation, which may be utilized for the generation and restoration of other intricate tissues and organs.

ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy.

Diabetes nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide, and podocyte injury is the central contributor to the progression of DN. Despite the emerging evidence that has established the importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of DN, abnormal protein O-GlcNAcylation is also augmented. Currently, the mechanism associating these two hyperglycemia-induced disorders remains poorly understood. This study intended to elucidate whether ER stress drives hyper-protein O-GlcNAcylation to cause podocyte injury in DN. We used both type 1 and type 2 DN models to confirm the occurrence of ER stress and excessive protein O-GlcNAcylation, and then podocyte purification was also conducted for further investigation. Nephroseq V5 data were mined and in vitro studies were applied to reveal the involvement of ER stress and hyper-O-GlcNAcylation in podocyte injury. Our results indicated that ER stress was induced in both type 1 and type 2 DN, and the human RNA-seq data from Nephroseq V5 showed that O-GlcNAcylation-related genes were significantly upregulated in the DN patients. We further demonstrated that ER stress occurred prior to hyper-O-GlcNAc modification and that pharmacologically inhibited protein O-GlcNAcylation can help decrease the podocyte apoptosis induced by hyperglycemia. Together, these discoveries will aid in uncovering the activation of the ER stress-O-GlcNAcylation axis in podocyte injury under DN, which will help open up new therapeutic approaches for preventing DN progression.

Unsupervisedly Prompting AlphaFold2 for Accurate Few-Shot Protein Structure Prediction.

Data-driven predictive methods that can efficiently and accurately transform protein sequences into biologically active structures are highly valuable for scientific research and medical development. Determining an accurate folding landscape using coevolutionary information is fundamental to the success of modern protein structure prediction methods. As the state of the art, AlphaFold2 has dramatically raised the accuracy without performing explicit coevolutionary analysis. Nevertheless, its performance still shows strong dependence on available sequence homologues. Based on the interrogation on the cause of such dependence, we presented EvoGen, a meta generative model, to remedy the underperformance of AlphaFold2 for poor MSA targets. By prompting the model with calibrated or virtually generated homologue sequences, EvoGen helps AlphaFold2 fold accurately in the low-data regime and even achieve encouraging performance with single-sequence predictions. Being able to make accurate predictions with few-shot MSA not only generalizes AlphaFold2 better for orphan sequences but also democratizes its use for high-throughput applications. Besides, EvoGen combined with AlphaFold2 yields a probabilistic structure generation method that could explore alternative conformations of protein sequences, and the task-aware differentiable algorithm for sequence generation will benefit other related tasks including protein design.

Unraveling the functional dark matter through global metagenomics.

Metagenomes encode an enormous diversity of proteins, reflecting a multiplicity of functions and activities1,2. Exploration of this vast sequence space has been limited to a comparative analysis against reference microbial genomes and protein families derived from those genomes. Here, to examine the scale of yet untapped functional diversity beyond what is currently possible through the lens of reference genomes, we develop a computational approach to generate reference-free protein families from the sequence space in metagenomes. We analyse 26,931 metagenomes and identify 1.17 billion protein sequences longer than 35 amino acids with no similarity to any sequences from 102,491 reference genomes or the Pfam database3. Using massively parallel graph-based clustering, we group these proteins into 106,198 novel sequence clusters with more than 100 members, doubling the number of protein families obtained from the reference genomes clustered using the same approach. We annotate these families on the basis of their taxonomic, habitat, geographical and gene neighbourhood distributions and, where sufficient sequence diversity is available, predict protein three-dimensional models, revealing novel structures. Overall, our results uncover an enormously diverse functional space, highlighting the importance of further exploring the microbial functional dark matter.

Role of Ultrasonic Microbubbles in Treating Rheumatoid Arthritis: Enhancing the Efficacy of Tocilizumab via Contrast-Enhanced Ultrasound-Monitored, Ultrasound-Targeted Microbubble Destruction.

OBJECTIVE: Our aim was to explore the feasibility of using ultrasound-targeted microbubble destruction (UTMD) to deliver tocilizumab and enhance its efficacy in treating rheumatoid arthritis (RA). METHODS: Rats with adjuvant-induced arthritis were randomly assigned to one of five treatment groups: group 1, tocilizumab + microbubbles (MBs) + UTMD; group 2, tocilizumab + MBs; group 3, tocilizumab + saline; group 4, MBs + UTMD; group 5, no treatment. We employed a commercially available ultrasound (US) machine capable of performing contrast-enhanced ultrasound (CEUS) and UTMD simultaneously using a single probe. CEUS was performed to monitor the entry and collapse of MBs. After treatment, the rats' left hindlimb paws were harvested for immunohistochemical staining of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). RESULTS: After injection of the mixture of drugs and MBs with UTMD, significant enhancement was seen in the inflamed hindlimb paw regions, which subsided immediately on exposure to low-frequency US beams and re-appeared in the intervals between beam exposures. IL-6 expression was significantly lower in groups 1, 2 and 3 than in groups 4 and 5 (p < 0.01). Group 1 had the lowest level of IL-6 expression (p [G1 vs. G2] < 0.01, p [G1 vs. G3] < 0.01). The levels of TNF-α expression in groups 1, 2, and 3 were significantly lower than those in groups 4 and 5, but no difference was observed in these levels between groups 1-3. CONCLUSION: UTMD shows promise in enhancing the treatment efficacy of anti-IL-6 drugs for RA treatment.

Implantable microfluidics: methods and applications.

Implantable microfluidics involves integrating microfluidic functionalities into implantable devices, such as medical implants or bioelectronic devices, revolutionizing healthcare by enabling personalized and precise diagnostics, targeted drug delivery, and regeneration of targeted tissues or organs. The impact of implantable microfluidics depends heavily on advancements in both methods and applications. Despite significant progress in the past two decades, continuous advancements are still required in fluidic control and manipulation, device miniaturization and integration, biosafety considerations, as well as the development of various application scenarios to address a wide range of healthcare issues. In this review, we discuss advancements in implantable microfluidics, focusing on methods and applications. Regarding methods, we discuss progress made in fluid manipulation, device fabrication, and biosafety considerations in implantable microfluidics. In terms of applications, we review advancements in using implantable microfluidics for drug delivery, diagnostics, tissue engineering, and energy harvesting. The purpose of this review is to expand research ideas for the development of novel implantable microfluidic devices for various healthcare applications.

Contactless acoustic tweezer for droplet manipulation on superhydrophobic surfaces.

Droplet manipulation on superhydrophobic surfaces (DMSS) without conventional pipetting is an emerging liquid handling technology, which can be potentially used for diagnostic, analysis, and synthetic processes. Despite notable progress, controlling droplet motion on superhydrophobic surfaces by contactless acoustic waves is rarely reported. Herein, we report a contactless acoustic tweezer (CAT) for DMSS based on establishing ultrasonic standing wave between an ultrasound transducer (UST) and a superhydrophobic substrate to manipulate droplets without physical contact. The CAT utilizes acoustic radiation forces to trap and move droplets on superhydrophobic surfaces, which allows for precise and controllable movement of droplets by controlling the movement of the UST. Small droplets with volume less than 20 µL can be levitated in mid-air for out-plane manipulation, and large droplets with volume up to 500 µL can be trapped for in-plane manipulation. Experimental results demonstrate the versatility of the CAT for manipulating droplets with various compositions and volumes on various superhydrophobic substrates, offering a versatile and cross-contamination-free liquid handling approach for applications, including but not limited to high-throughput surface-enhanced Raman scattering.

Design and numerical study of a bidirectional acoustic microfluidic pump enabled by microcantilever arrays.

Microfluidics offers a versatile and promising platform for various applications in biomedical and other fields, boasting cost-effectiveness, rapid analysis time, and a compact equipment footprint. However, achieving controlled and versatile microfluidic motion within implantable devices presents a significant challenge. In this study, we propose a novel bidirectional micro-pump design that leverages two sharp-edge microcantilever arrays, driven by ultrasound, to enable selective flow direction by manipulating the ultrasound frequency. Through systematic numerical simulation, we demonstrate the feasibility of this design and further optimize its performance through comprehensive parametric analysis. This work provides valuable guidance for the practical development of sharp-edge-based acoustic micro-pumps, particularly for potential implantable applications such as controlled drug release and in vivo sampling for advanced diagnostics.

Batch Fabrication of Paper-Based Waterproof Flexible Pressure Sensors Enabled by Roll-to-Roll Lamination.

Paper is a green and porous material that has been widely used in flexible pressure sensors due to its flexibility, renewability, and lightness. However, these sensors are often susceptible to environmental factors such as moisture and chemicals, leading to degradation or failure of their reliability for practical applications. Herein, we present a roll-to-roll lamination strategy for batch fabrication of paper-based waterproof flexible pressure sensors with good consistency based on single-walled carbon nanotube (SWCNT) coated tissue paper pieces. The pieces are sandwiched between poly(ethylene glycol) terephthalate (PET) films with a hot melt adhesive and screen-printed electrodes, and the layers are bonded reliably using roll-to-roll lamination. This process allows for the rapid fabrication of a batch of waterproof, flexible pressure sensors with high stability over 5000 loading/unloading cycles, an ultrashort response time of 8 ms, and a wide measurement range (450 kPa). These features enable our sensor to be utilized for human physiological signal detection, motion tracking, and drowning detection. Furthermore, the process also allows for the fabrication of sensor arrays for spatial pressure mapping and real-time human-machine interaction, expanding the application field of paper-based pressure sensors. This proposed batch fabrication strategy greatly enhances the consistency and reliability of paper-based pressure sensors, demonstrating endless possibilities for paper-based pressure sensors to be used for various applications.