PUF Proteins as Critical RNA-Binding Proteins in TriTryp Parasites: A Review Article.

In eukaryotes, translation is a fundamental step in the long pathway of protein synthesis within the cell. In this process, several proteins and factors have involved directly or indirectly, individually or in association with other elements to contact mRNA. For perfect translation, many essential modifications should be done, such as cis-splicing to remove introns and two main events for capping and poly A polymerization in 5' and 3' end of mRNA, respectively. Gene expression is then regulated at both translation and stability of the target mRNA molecule levels. Pumilio/FBFs (PUFs) are the main group of RNA-binding proteins which bind to the 3'-UTR of target RNA and thereby regulate the fate, stability and subcellular localization of mRNAs and adjust the translated protein level. PUF proteins have been found both in nucleus where that bind to precursor mRNA, for processing and maturation of rRNA, and in cytoplasm where that bind to mRNA, stall the ribosomes, suppress the translation and localization of the mRNA. They can regulate the expression of mRNAs through activation or suppression of translation. Therefore, these proteins have recently garnered much attention as new generation of therapeutic targets against diseases such as cancer and neurological disorders. In comparison to other eukaryotes, trypanosomatids have a high number of PUF proteins, which function not only as gene expression regulatory factors but also in several biological processes such as differentiation and life-cycle progression of the cells. Here, we review the molecular and biological roles of known PUF proteins in TriTryp parasites (Trypanosome brucei, T. cruzi and Leishmania) beside some other parasites.

A Case Report of Verheij Syndrome.

Verheij syndrome (VRJS) is a rare genetic disorder characterized by a range of developmental issues and physical abnormalities. This condition is caused by mutations or deletions in the PUF60 (poly-U-binding factor 60 kDa) gene, which is located on the long arm of chromosome 8, specifically in the q24.3 region. We present a unique case of an 11-year-old girl child with VRJS. The child presented with absence seizures. She was noted to have short stature, spina bifida of the lower cervical vertebrae, and a smaller right kidney on ultrasonography. This case expands the phenotypic spectrum of VRJS by demonstrating a milder presentation, highlighting the importance of a high index of suspicion for the diagnosis, even in atypical presentations. Whole exome sequencing identified the causative mutation, confirming the diagnosis. Growth hormone therapy was initiated for short stature but discontinued due to the subsequent development of idiopathic intracranial hypertension. Additionally, this report represents the first documented case of VRJS in India, emphasizing the importance of global data sharing and collaboration for improving the understanding and management of rare genetic disorders.

A robust deep learning attack immune MRAM-based physical unclonable function.

The ubiquitous presence of electronic devices demands robust hardware security mechanisms to safeguard sensitive information from threats. This paper presents a physical unclonable function (PUF) circuit based on magnetoresistive random access memory (MRAM). The circuit utilizes inherent characteristics arising from fabrication variations, specifically magnetic tunnel junction (MTJ) cell resistance, to produce corresponding outputs for applied challenges. In contrast to Arbiter PUF, the proposed effectively satisfies the strict avalanche criterion (SAC). Additionally, the grid-like structure of the proposed circuit preserves its resistance against machine learning-based modeling attacks. Various machine learning (ML) attacks employing multilayer perceptron (MLP), linear regression (LR), and support vector machine (SVM) networks are simulated for two-array and four-array architectures. The MLP-attack prediction accuracy was 53.61% for a two-array circuit and 49.87% for a four-array circuit, showcasing robust performance even under the worst-case process variations. In addition, deep learning-based modeling attacks in considerable high dimensions utilizing multiple networks such as convolutional neural network (CNN), recurrent neural network (RNN), MLP, and Larq are used with the accuracy of 50.31%, 50.25%, 50.31%, and 50.31%, respectively. The efficiency of the proposed circuit at the layout level is also investigated for simplified two-array architecture. The simulation results indicate that the proposed circuit offers intra and inter-hamming distance (HD) with a mean of 0.98% and 49.96%, respectively, and a mean diffuseness of 49.09%.

PUF3 RNA binding protein of Trypanosoma cruzi regulates mitochondrial morphology and function.

The RNA-binding PUF proteins are post-transcriptional regulators found throughout the eukaryotic domain. In Trypanosoma cruzi, ten Puf genes termed Puf1 to Puf10 have been identified. Considering that the control of gene expression in this parasite is mainly at the post-transcriptional level, we characterized the PUF3 protein by knocking out and overexpressing the gene in T. cruzi epimastigotes and studied different genetic and biological features. The RNA-seq analyses in both genotypes showed significant changes in the number of regulated transcripts compared with wild-type parasites. Thus, the number of differentially expressed genes in the knockout (ΔTcPuf3) and the overexpressor (pTEXTcPuf3) were 238 and 187, respectively. In the knockout, a more significant proportion of genes was negatively regulated (166 out of 238). In contrast, in the overexpressor, positively regulated genes were predominant (149 out of 170). Additionally, when we predicted the subcellular location of the differentially expressed genes, the results revealed an important representation of nuclear genes encoding mitochondrial proteins. Therefore, we determined whether overexpression or knockout of TcPuf3 could lead to changes in both mitochondrial structure and cellular respiration. When mitochondria from ΔTcPuf3 and pTEXTcPuf3 parasites were analyzed by transmission electron microscopy (TEM), it was observed that the overexpressor had an abnormal mitochondrial morphology, evidenced by swelling. The results associated with cellular respiration showed that both the ΔTcPuf3 and pTEXTcPuf3 had a lower efficiency in routine respiration and the electron transport system capacity. Likewise, the mitochondria from overexpressing parasites showed a slight hyperpolarization. Additionally, several biological features, depending on the function of the mitochondria, were altered, such as growth, cell division, metacyclogenesis, ROS production, and response to benznidazole. In conclusion, our results suggest that although PUF3 is not an essential protein in T. cruzi, it influences mitochondrial transcripts, affecting mitochondrial morphology and function.

Flexible Physical Unclonable Functions Based on Non-deterministically Distributed Dye-Doped Fibers and Droplets.

The development of new anticounterfeiting solutions is a constant challenge and involves several research fields. Much interest is currently devoted to systems that are impossible to clone, based on the physical unclonable function (PUF) paradigm. In this work, a new strategy based on electrospinning and electrospraying of dye-doped polymeric materials is presented for the manufacturing of flexible free-standing films that embed simultaneously different PUF keys. The proposed films can be used to fabricate novel anticounterfeiting labels having three encryption levels: (i) a map of fluorescent polymer droplets, with random positions on a dense yarn of polymer nanofibers, (ii) a characteristic fluorescence spectrum for each label, and (iii) the unique speckle patterns that every label produces when illuminated with coherent laser light shaped in different wavefronts. The intrinsic uniqueness introduced by the manufacturing process encodes enough complexity into the optical anticounterfeiting tag to generate thousands of cryptographic keys. The simple and cheap fabrication process as well as multilevel authentication makes such colored polymeric unclonable tags a practical solution in the secure protection of goods in our daily life.

ZnO/PUF composites with a large capacity for phosphate adsorption: adsorption behavior and mechanism studies.

Phosphate is present in all kinds of industrial wastewater; how to remove it to meet the strict total phosphorus discharge standards is a challenge. This study used a one-step foaming technique to fill polyurethane foam (PUF) with ZnO, taking advantage of PUF's excellent features like its porous network, lightweight, hydrophilicity, and abundance of binding sites to create ZnO/PUF composites with high adsorption capacity and exceptional separation properties. The adsorption isotherms, kinetics, starting pH, and matrix impacts of ZnO/PUF composites on phosphate were examined in batch studies. The results showed that the composites had good adsorption performance for phosphate with a saturated adsorption capacity of 460.25 mg/g. The quasi-secondary kinetic and Langmuir models could better describe the adsorption process, which belonged to the chemical adsorption of monomolecular layers. The composites' ability to treat phosphates in complicated waters was shown by their ability to retain a high adsorption capacity in the pH range of 3-6. In column experiments, the composite also maintains a good affinity for phosphate during dynamic adsorption. Multiple characterizations indicate that the adsorption mechanism is a combined effect of ligand exchange and electrostatic interactions. Therefore, this study provides valuable insights for practical phosphorus-containing wastewater treatment.

C. elegans Germline as Three Distinct Tumor Models.

Tumor cells display abnormal growth and division, avoiding the natural process of cell death. These cells can be benign (non-cancerous growth) or malignant (cancerous growth). Over the past few decades, numerous in vitro or in vivo tumor models have been employed to understand the molecular mechanisms associated with tumorigenesis in diverse regards. However, our comprehension of how non-tumor cells transform into tumor cells at molecular and cellular levels remains incomplete. The nematode C. elegans has emerged as an excellent model organism for exploring various phenomena, including tumorigenesis. Although C. elegans does not naturally develop cancer, it serves as a valuable platform for identifying oncogenes and the underlying mechanisms within a live organism. In this review, we describe three distinct germline tumor models in C. elegans, highlighting their associated mechanisms and related regulators: (1) ectopic proliferation due to aberrant activation of GLP-1/Notch signaling, (2) meiotic entry failure resulting from the loss of GLD-1/STAR RNA-binding protein, (3) spermatogenic dedifferentiation caused by the loss of PUF-8/PUF RNA-binding protein. Each model requires the mutations of specific genes (glp-1, gld-1, and puf-8) and operates through distinct molecular mechanisms. Despite these differences in the origins of tumorigenesis, the internal regulatory networks within each tumor model display shared features. Given the conservation of many of the regulators implicated in C. elegans tumorigenesis, it is proposed that these unique models hold significant potential for enhancing our comprehension of the broader control mechanisms governing tumorigenesis.

A higher order PUF complex is central to regulation of C. elegans germline stem cells.

PUF RNA-binding proteins are broadly conserved stem cell regulators. Nematode PUF proteins maintain germline stem cells (GSCs) and, with key partner proteins, repress differentiation mRNAs, including gld-1. Here we report that PUF protein FBF-2 and its partner LST-1 form a ternary complex that represses gld-1 via a pair of adjacent FBF-2 binding elements (FBEs) in its 3ÚTR. One LST-1 molecule links two FBF-2 molecules via motifs in the LST-1 intrinsically-disordered region; the gld-1 FBE pair includes a well-established 'canonical' FBE and a newly-identified noncanonical FBE. Remarkably, this FBE pair drives both full RNA repression in GSCs and full RNA activation upon differentiation. Discovery of the LST-1-FBF-2 ternary complex, the gld-1 adjacent FBEs, and their in vivo significance predicts an expanded regulatory repertoire of different assemblies of PUF-partner complexes in nematode germline stem cells. It also suggests analogous PUF controls may await discovery in other biological contexts and organisms.

Two-Layered Multi-Factor Authentication Using Decentralized Blockchain in an IoT Environment.

Internet of Things (IoT) technology is evolving over the peak of smart infrastructure with the participation of IoT devices in a wide range of applications. Traditional IoT authentication methods are vulnerable to threats due to wireless data transmission. However, IoT devices are resource- and energy-constrained, so building lightweight security that provides stronger authentication is essential. This paper proposes a novel, two-layered multi-factor authentication (2L-MFA) framework using blockchain to enhance IoT devices and user security. The first level of authentication is for IoT devices, one that considers secret keys, geographical location, and physically unclonable function (PUF). Proof-of-authentication (PoAh) and elliptic curve Diffie-Hellman are followed for lightweight and low latency support. Second-level authentication for IoT users, which are sub-categorized into four levels, each defined by specific factors such as identity, password, and biometrics. The first level involves a matrix-based password; the second level utilizes the elliptic curve digital signature algorithm (ECDSA); and levels 3 and 4 are secured with iris and finger vein, providing comprehensive and robust authentication. We deployed fuzzy logic to validate the authentication and make the system more robust. The 2L-MFA model significantly improves performance, reducing registration, login, and authentication times by up to 25%, 50%, and 25%, respectively, facilitating quicker cloud access post-authentication and enhancing overall efficiency.

Highly Reliable Magnetic Memory-Based Physical Unclonable Functions.

Magnetic random-access memory (MRAM), which stores information through control of the magnetization direction, offers promising features as a viable nonvolatile memory alternative, including high endurance and successful large-scale commercialization. Recently, MRAM applications have extended beyond traditional memories, finding utility in emerging computing architectures such as in-memory computing and probabilistic bits. In this work, we report highly reliable MRAM-based security devices, known as physical unclonable functions (PUFs), achieved by exploiting nanoscale perpendicular magnetic tunnel junctions (MTJs). By intentionally randomizing the magnetization direction of the antiferromagnetically coupled reference layer of the MTJs, we successfully create an MRAM-PUF. The proposed PUF shows ideal uniformity and uniqueness and, in particular, maintains performance over a wide temperature range from -40 to +150 °C. Moreover, rigorous testing with more than 1584 challenge-response pairs of 64 bits each confirms resilience against machine learning attacks. These results, combined with the merits of commercialized MRAM technology, would facilitate the implementation of MRAM-PUFs.

Identification of a de novo PUF60 variant associated with craniofacial microsomia.

Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, is a congenital disorder characterized by hypoplasia of the mandible and external ear due to tissue malformations originating from the first and second branchial arches. However, distinguishing it from other syndromes of branchial arch abnormalities is difficult, and causal variants remain unidentified in many cases. In this report, we performed an exome sequencing analysis of a Brazilian family with CFM. The proband was a 12-month-old boy with clinical findings consistent with the diagnostic criteria for CFM, including unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities. A heterozygous de novo nonsense variant (c.713C>G, p.S238*) in PUF60 was identified, which was predicted to be pathogenic in silico. PUF60 has been reported as a causal gene in Verheij syndrome, but not in CFM. Although the boy showed craniofacial abnormalities and developmental delay that overlapped with Verheij syndrome, the facial asymmetry with unilateral hypoplasia of the mandible observed in this case did not match the previously reported phenotypes of PUF60 variants. Our findings expand the phenotypic range of PUF60 variants that cover CFM and Verheij syndrome.

On the Aging of OTFTs and Its Impact on PUFs Reliability.

Given the current maturity of printed technologies, Organic Thin-Film Transistors (OTFT) still show high initial variability, which can be beneficial for its exploitation in security applications. In this work, the process-related variability and aging of commercial OTFTs have been characterized to evaluate the feasibility of OTFTs-based Physical Unclonable Functions (PUFs) implementation. For our devices, ID-based PUFs show good uniformity and uniqueness. However, PUFs' reliability could be compromised because of the observed transient and aging effects in the OTFTs, which could hinder the reproducibility of the generated fingerprints. A systematic study of the aging of OTFTs has been performed to evaluate the PUFs' reliability. Our results suggest that the observed transient and aging effects could be mitigated so that the OTFTs-based PUFs' reliability could be improved.

Secure ECDSA SRAM-PUF Based on Universal Single/Double Scalar Multiplication Architecture.

Physically unclonable functions (PUFs) are crucial for enhancing cybersecurity by providing unique, intrinsic identifiers for electronic devices, thus ensuring their authenticity and preventing unauthorized cloning. The SRAM-PUF, characterized by its simple structure and ease of implementation in various scenarios, has gained widespread usage. The soft-decision Reed-Muller (RM) code, an error correction code, is commonly employed in these designs. This paper introduces the design of an RM code soft-decision attack algorithm to reveal its potential security risks. To address this problem, we propose a soft-decision SRAM-PUF structure based on the elliptic curve digital signature algorithm (ECDSA). To improve the processing speed of the proposed secure SRAM-PUF, we propose a custom ECDSA scheme. Further, we also propose a universal architecture for the critical operations in ECDSA, elliptic curve scalar multiplication (ECSM), and elliptic curve double scalar multiplication (ECDSM) based on the differential addition chain (DAC). For ECSMs, iterations can be performed directly; for ECDSMs, a two-dimensional DAC is constructed through precomputation, followed by iterations. Moreover, due to the high similarity of ECSM and ECDSM data paths, this universal architecture saves hardware resources. Our design is implemented on a field-programmable gate array (FPGA) and an application-specific integrated circuit (ASIC) using a Xilinx Virtex-7 and an TSMC 40 nm process. Compared to existing research, our design exhibits a lower bit error rate (2.7×10-10) and better area-time performance (3902 slices, 6.615 µs ECDSM latency).

PUF60 loss-of-function with normal cognition should be considered in the differential diagnosis of Klippel-Feil syndrome.

Klippel-Feil syndrome (KFS) has a genetically heterogeneous phenotype with six known genes, exhibiting both autosomal dominant and autosomal recessive inheritance patterns. PUF60 is a nucleic acid-binding protein, which is involved in a number of nuclear processes, including pre-mRNA splicing, apoptosis, and transcription regulation. Pathogenic variants in this gene have been described in Verheij syndrome due to either 8q24.3 microdeletion or PUF60 single-nucleotide variants. PUF60-associated conditions usually include intellectual disability, among other findings, some overlapping KFS; however, PUF60 is not classically referred to as a KFS gene. Here, we describe a 6-year-old female patient with clinically diagnosed KFS and normal cognition, who harbors a heterozygous de novo variant in the PUF60 gene (c.1179del, p.Ile394Serfs*7). This is a novel frameshift variant, which is predicted to result in a premature stop codon. Clinically, our patient demonstrates a pattern of malformations that matches reported cases of PUF60 variants; however, unlike most others, she has no clear learning difficulties. In light of these findings, we propose that PUF60 should be considered in the differential diagnosis of KFS and that normal cognition should not exclude its testing.

PUFchain 3.0: Hardware-Assisted Distributed Ledger for Robust Authentication in Healthcare Cyber-Physical Systems.

This article presents a novel hardware-assisted distributed ledger-based solution for simultaneous device and data security in smart healthcare. This article presents a novel architecture that integrates PUF, blockchain, and Tangle for Security-by-Design (SbD) of healthcare cyber-physical systems (H-CPSs). Healthcare systems around the world have undergone massive technological transformation and have seen growing adoption with the advancement of Internet-of-Medical Things (IoMT). The technological transformation of healthcare systems to telemedicine, e-health, connected health, and remote health is being made possible with the sophisticated integration of IoMT with machine learning, big data, artificial intelligence (AI), and other technologies. As healthcare systems are becoming more accessible and advanced, security and privacy have become pivotal for the smooth integration and functioning of various systems in H-CPSs. In this work, we present a novel approach that integrates PUF with IOTA Tangle and blockchain and works by storing the PUF keys of a patient's Body Area Network (BAN) inside blockchain to access, store, and share globally. Each patient has a network of smart wearables and a gateway to obtain the physiological sensor data securely. To facilitate communication among various stakeholders in healthcare systems, IOTA Tangle's Masked Authentication Messaging (MAM) communication protocol has been used, which securely enables patients to communicate, share, and store data on Tangle. The MAM channel works in the restricted mode in the proposed architecture, which can be accessed using the patient's gateway PUF key. Furthermore, the successful verification of PUF enables patients to securely send and share physiological sensor data from various wearable and implantable medical devices embedded with PUF. Finally, healthcare system entities like physicians, hospital admin networks, and remote monitoring systems can securely establish communication with patients using MAM and retrieve the patient's BAN PUF keys from the blockchain securely. Our experimental analysis shows that the proposed approach successfully integrates three security primitives, PUF, blockchain, and Tangle, providing decentralized access control and security in H-CPS with minimal energy requirements, data storage, and response time.

Novel Genetic and Phenotypic Expansion in Ameliorated PUF60-Related Disorders.

Heterozygous variants in the Poly(U) Binding Splicing Factor 60kDa gene (PUF60) have been associated with Verheij syndrome, which has the key features of coloboma, short stature, skeletal abnormalities, developmental delay, palatal abnormalities, and congenital heart and kidney defects. Here, we report five novel patients from unrelated families with PUF60-related disorders exhibiting novel genetic and clinical findings with three truncating variants, one splice-site variant with likely reduced protein expression, and one missense variant. Protein modeling of the patient's missense variant in the PUF60 AlphaFold structure revealed a loss of polar bonds to the surrounding residues. Neurodevelopmental disorders were present in all patients, with variability in speech, motor, cognitive, social-emotional and behavioral features. Novel phenotypic expansions included movement disorders as well as immunological findings with recurrent respiratory, urinary and ear infections, atopic diseases, and skin abnormalities. We discuss the role of PUF60 in immunity with and without infection based on recent organismic and cellular studies. As our five patients showed less-severe phenotypes than classical Verheij syndrome, particularly with the absence of key features such as coloboma or palatal abnormalities, we propose a reclassification as PUF60-related neurodevelopmental disorders with multi-system involvement. These findings will aid in the genetic counseling of patients and families.

PUF partner interactions at a conserved interface shape the RNA-binding landscape and cell fate in Caenorhabditis elegans.

Protein-RNA regulatory networks underpin much of biology. C. elegans FBF-2, a PUF-RNA-binding protein, binds over 1,000 RNAs to govern stem cells and differentiation. FBF-2 interacts with multiple protein partners via a key tyrosine, Y479. Here, we investigate the in vivo significance of partnerships using a Y479A mutant. Occupancy of the Y479A mutant protein increases or decreases at specific sites across the transcriptome, varying with RNAs. Germline development also changes in a specific fashion: Y479A abolishes one FBF-2 function-the sperm-to-oocyte cell fate switch. Y479A's effects on the regulation of one mRNA, gld-1, are critical to this fate change, though other network changes are also important. FBF-2 switches from repression to activation of gld-1 RNA, likely by distinct FBF-2 partnerships. The role of RNA-binding protein partnerships in governing RNA regulatory networks will likely extend broadly, as such partnerships pervade RNA controls in virtually all metazoan tissues and species.

Biocompatible optical physically unclonable function hydrogel microparticles for on-dose authentication.

On-dose authentication (ODA) enhances security by incorporating customized molecular or micro-tags into each pill, preventing counterfeit products in genuine packages. ODA's security relies on tag non-replication and non-reverse engineering. Combining ODA with graphical Physical Unclonable Functions (PUF) promises maximum security. PUF uses intrinsic micro or nanoscale randomness as a unique 'fingerprint'. However, current graphical PUFs have limitations like specific illumination requirements and the use of toxic materials, restricting their use in pharmaceuticals. In this study, we propose a novel approach called on-dose PUF. This method involves embedding microspheres randomly within micro biocompatible hydrogel particles. We showcase two distinct types of such on-dose PUFs. The first type utilizes randomly distributed superparamagnetic colloids (SPC) of identical diameters, while the second type utilizes vortexed sunflower oil drops of various diameters. The diameter and coordinates of the microspheres serve as input for generating cryptographic keys. A universal circle identification and binning program is used for extracting this information. One advantage of this approach is that it enables imaging using white light illumination and low-magnification microscopy, as color and signal intensity information are not crucial. This method enables patients to verify their medication by using their mobile phones from home. To assess the performance of the proposed on-dose PUF, we conducted canonical investigations on the single-diameter system. This system can only generate one layer of cryptographic keys, making it potentially more vulnerable than the multiple-diameter system. However, the single-diameter system successfully passed NIST Statistical tests and exhibited sufficient randomness, ideal bit uniformity, Hamming distance, and device uniqueness. Furthermore, we found that the encoding capacity of the single-diameter system was 9.2×1018, providing ample labeling potential.

Targeting PUF60 prevents tumor progression by retarding mRNA decay of oxidative phosphorylation in ovarian cancer.

PURPOSE: Ovarian cancer (OC) is the leading cause of death from gynecological malignancies, and its etiology and pathogenesis are currently unclear. Recent studies have found that PUF60 overexpressed in various cancers. However, the exact function of PUF60 in global RNA processing and its role in OC has been unclear. METHODS: The expression of PUF60 and its relationship with clinical characteristics were analyzed by multiple database analysis and immunohistochemistry. Phenotypic effects of PUF60 on ovarian cancer cell proliferation and metastasis were examined by in vitro cell proliferation assay, migration assay, and in vivo xenograft models and lung metastasis models. RNA immunoprecipitation, seahorse analyses, RNA stability assay were used to study the effect of PUF60 on the stability of oxidative phosphorylation (OXPHOS)-related genes in OC. RESULTS: We report PUF60 is highly expressed in OC with frequent amplification of up to 33.9% and its upregulation predicts a poor prognosis. PUF60 promotes the proliferation and migration of OC cells both in vitro and in vivo. Mechanistically, we demonstrated that silencing of PUF60 enhanced the stability of mRNA transcripts involved in OXPHOS and decreased the formation of processing bodies (P-bodies), ultimately elevating the OXPHOS level. CONCLUSION: Our study unveils a novel function of PUF60 in OC energy metabolism. Thus, PUF60 may serve as a novel target for the treatment of patients with OC.

The use of simple structural parameters of organic compounds to assess their PUF-air partition coefficients.

A novel approach is introduced for the reliable prediction of PUF-air partition coefficients of organic compounds, which can determine the environmental fate of organic compounds during interactions with air, soil, and water. The biggest accessible measured data of PUF-air partition coefficients for 170 chemicals are used to develop and test the novel model. In comparison to available quantitative structure-property relationship (QSPR) methods for the prediction of PUF-air partition coefficients that need complex descriptors, the here used descriptors are simpler. The assessed various statistical factors of the simple method containing 147 (training) and 23 (test) organic compounds can verify the external and internal cross-validations. Various statistical parameters confirm the high reliability of the novel model as compared with the outputs of complex multiple linear regression (MLR), artificial neural network (ANN) and support vector machine (SVM) methods. The values of R-squared (R2), and root mean square error (RMSE) of the new model are for training/test sets are 0.924/0.894 and 0.374/0.318, respectively. Meanwhile, R2 and RMSE values for three comparative models training/test sets are (i) MLR: 0.848/0.670 (R2) and 0.531/0.573 (RMSE); (ii) ANN: 0.902/0.664 (R2) and 0.425/0.560 (RMSE); (iii) SVM: 0.935/0.794 (R2) and 0.351/0.419 (RMSE). Thus, the new model the simplest approach with higher reliability in comparison to the best available methods.