Smart Physical-Based Transdermal Drug Delivery System:Towards Intelligence and Controlled Release.

Transdermal drug delivery systems based on physical principles have provided a stable, efficient, and safe strategy for disease therapy. However, the intelligent device with real-time control and precise drug release is required to enhance treatment efficacy and improve patient compliance. This review summarizes the recent developments, application scenarios, and drug release characteristics of smart transdermal drug delivery systems fabricated with physical principle. Special attention is paid to the progress of intelligent design and concepts in of physical-based transdermal drug delivery technologies for real-time monitoring and precise drug release. In addition, facing with the needs of clinical treatment and personalized medicine, the recent progress and trend of physical enhancement are further highlighted for transdermal drug delivery systems in combination with pharmaceutical dosage forms to achieve better transdermal effects and facilitate the development of smart medical devices. Finally, the next generation and future application scenarios of smart physical-based transdermal drug delivery systems are discussed, a particular focus in vaccine delivery and tumor treatment.

Gate-Tunable Critical Current of the Three-Dimensional Niobium Nanobridge Josephson Junction.

Recent studies have shown that the critical currents of several metallic superconducting nanowires and Dayem bridges can be locally tuned by using a gate voltage (Vg). Here, we report a gate-tunable Josephson junction structure constructed from a three-dimensional (3D) niobium nanobridge junction (NBJ) with a voltage gate on top. Measurements up to 6 K showed that the critical current of this structure can be tuned to zero by increasing Vg. The critical gate voltage was reduced to 16 V and may possibly be reduced further by reducing the thickness of the insulation layer between the gate and the NBJ. Furthermore, the flux modulation generated by Josephson interference of two parallel 3D NBJs can also be tuned by using Vg in a similar manner. Therefore, we believe that this gate-tunable Josephson junction structure is promising for superconducting circuit fabrication at high integration levels.

Helical Luttinger Liquid on the Edge of a Two-Dimensional Topological Antiferromagnet.

A boundary helical Luttinger liquid (HLL) with broken bulk time-reversal symmetry belongs to a unique topological class that may occur in antiferromagnets (AFM). Here, we search for signatures of HLL on the edge of a recently discovered topological AFM, MnBi2Te4 even-layer. Using a scanning superconducting quantum interference device, we directly image helical edge current in the AFM ground state appearing at its charge neutral point. Such a helical edge state accompanies an insulating bulk which is topologically distinct from the ferromagnetic Chern insulator phase, as revealed in a magnetic field driven quantum phase transition. The edge conductance of the AFM order follows a power law as a function of temperature and source-drain bias which serves as strong evidence for HLL. Such HLL scaling is robust at finite fields below the quantum critical point. The observed HLL in a layered AFM semiconductor represents a highly tunable topological matter compatible with future spintronics and quantum computation.

The role of gut microbiota in MP/NP-induced toxicity.

Microplastics (MPs) and nanoplastics (NPs) are globally recognized as emerging environmental pollutants in various environmental media, posing potential threats to ecosystems and human health. MPs/NPs are unavoidably ingested by humans, mainly through contaminated food and drinks, impairing the gastrointestinal ecology and seriously impacting the human body. The specific role of gut microbiota in the gastrointestinal tract upon MP/NP exposure remains unknown. Given the importance of gut microbiota in metabolism, immunity, and homeostasis, this review aims to enhance our current understanding of the role of gut microbiota in MP/NP-induced toxicity. First, it discusses human exposure to MPs/NPs through the diet and MP/NP-induced adverse effects on the respiratory, digestive, neural, urinary, reproductive, and immune systems. Second, it elucidates the complex interactions between the gut microbiota and MPs/NPs. MPs/NPs can disrupt gut microbiota homeostasis, while the gut microbiota can degrade MPs/NPs. Third, it reveals the role of the gut microbiota in MP/NP-mediated systematic toxicity. MPs/NPs cause direct intestinal toxicity and indirect toxicity in other organs via regulating the gut-brain, gut-liver, and gut-lung axes. Finally, novel approaches such as dietary interventions, prebiotics, probiotics, polyphenols, engineered bacteria, microalgae, and micro/nanorobots are recommended to reduce MP/NP toxicity in humans. Overall, this review provides a theoretical basis for targeting the gut microbiota to study MP/NP toxicity and develop novel strategies for its mitigation.

Engineering the cofactor binding site of 7α-hydroxysteroid dehydrogenase for improvement of catalytic activity, thermostability, and alteration of substrate preference.

Hydroxysteroid dehydrogenases (HSDHs) are crucial for bile acid metabolism and influence the size of the bile acid pool and gut microbiota composition. HSDHs with high activity, thermostability, and substrate selectivity are the basis for constructing engineered bacteria for disease treatment. In this study, we designed mutations at the cofactor binding site involving Thr15 and Arg16 residues of HSDH St-2-2. The T15A, R16A, and R16Q mutants exhibited 7.85-, 2.50-, and 4.35-fold higher catalytic activity than the wild type, respectively, while also displaying an altered substrate preference (from taurocholic acid (TCA) to taurochenodeoxycholic acid (TCDCA)). These mutants showed lower Km and higher kcat values, indicating stronger binding to the substrate and resulting in 3190-, 3123-, and 3093-fold higher kcat/Km values for TCDCA oxidation. Furthermore, the Tm values of the T15A, R16A, and R16Q mutants were found to increase by 4.3 °C, 6.0 °C, and 7.0 °C, respectively. Molecular structure analysis indicated that reshaped internal hydrogens and surface mutations could improve catalytic activity and thermostability, and altered interactions among the catalytic triad, cofactor binding sites, and substrates could change substrate preference. This work provides valuable insights into modifying substrate preference as well as enhancing the catalytic activity and thermostability of HSDHs by targeting the cofactor binding site.

Novel approaches in IBD therapy: targeting the gut microbiota-bile acid axis.

Inflammatory bowel disease (IBD) is a chronic and recurrent condition affecting the gastrointestinal tract. Disturbed gut microbiota and abnormal bile acid (BA) metabolism are notable in IBD, suggesting a bidirectional relationship. Specifically, the diversity of the gut microbiota influences BA composition, whereas altered BA profiles can disrupt the microbiota. IBD patients often exhibit increased primary bile acid and reduced secondary bile acid concentrations due to a diminished bacteria population essential for BA metabolism. This imbalance activates BA receptors, undermining intestinal integrity and immune function. Consequently, targeting the microbiota-BA axis may rectify these disturbances, offering symptomatic relief in IBD. Here, the interplay between gut microbiota and bile acids (BAs) is reviewed, with a particular focus on the role of gut microbiota in mediating bile acid biotransformation, and contributions of the gut microbiota-BA axis to IBD pathology to unveil potential novel therapeutic avenues for IBD.

Rational Design of Human Hair Keratin-Driven Proteins for Hair Growth Promotion.

Keratins, the most abundant proteins in human hair, are excellent hair nutrients for growth. However, the complex components of keratin extract hinder their mechanism investigation, and the pure recombinant keratin with poor solubility limited its hair growth promotion efficiency. Here, the water-soluble recombinant keratins (RKs) of K31 and K81 are rationally designed through QTY Code methodology, which are then used to fabricate the microneedles to study the effect of keratin on hair growth. Interestingly, it is discovered that more than 40% of the hair follicles (HFs) in the RK81QTY group entered the anagen on day 12 and the diameter of new hair is 15.10 ± 2.45 µm, which significantly promoted growth and development of HFs and improved new hair quality compared to RK31QTY. Water-soluble RKs significantly enhanced HFs activity and de novo regeneration of robust hairs compared to extract and minoxidil by upregulating the PI3K/AKT/Nf-κB signaling axis. These findings highlight the potential of designing solubilized recombinant keratins with distinct properties to improve therapeutical effects and open new avenues to designing keratin-based proteins.

Oscillating paramagnetic Meissner effect and Berezinskii-Kosterlitz-Thouless transition in underdoped Bi2Sr2CaCu2O8+δ.

Superconducting phase transitions in two dimensions lie beyond the description of the Ginzburg-Landau symmetry-breaking paradigm for three-dimensional superconductors. They are Berezinskii-Kosterlitz-Thouless (BKT) transitions of paired-electron condensate driven by the unbinding of topological excitations, i.e. vortices. The recently discovered monolayers of layered high-transition-temperature ([Formula: see text]) cuprate superconductor Bi2Sr2CaCu2O8+δ (Bi2212) meant that this 2D superconductor promised to be ideal for the study of unconventional superconductivity. But inhomogeneity posed challenges for distinguishing BKT physics from charge correlations in this material. Here, we utilize the phase sensitivity of scanning superconducting quantum interference device microscopy susceptometry to image the local magnetic response of underdoped Bi2212 from the monolayer to the bulk throughout its phase transition. The monolayer segregates into domains with independent phases at elevated temperatures below [Formula: see text]. Within a single domain, we find that the susceptibility oscillates with flux between diamagnetism and paramagnetism in a Fraunhofer-like pattern up to [Formula: see text]. The finite modulation period, as well as the broadening of the peaks when approaching [Formula: see text] from below, suggests well-defined vortices that are increasingly screened by the dissociation of vortex-antivortex plasma through a BKT transition. In the multilayers, the susceptibility oscillation differs in a small temperature regime below [Formula: see text], consistent with a dimensional crossover led by interlayer coupling. Serving as strong evidence for BKT transition in the bulk, we observe a sharp jump in phase stiffness and paramagnetism at small fields just below [Formula: see text]. These results unify the superconducting phase transitions from the monolayer to the bulk underdoped Bi2212, and can be collectively referred to as the BKT transition with interlayer coupling.

Status and Future Directions of Therapeutics and Prognosis of Cardiac Amyloidosis.

Accumulation of aberrant proteins in the heart causes cardiac amyloidosis, an uncommon and complicated illness. It can be classified into two main types: light chain (AL) and transthyretin (ATTR). The diagnosis of cardiac amyloidosis is challenging due to its non-specific clinical presentation and lack of definitive diagnostic tests. Diagnostic accuracy has increased with the advent of modern imaging methods, including cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET) scans. Depending on the severity of cardiac amyloidosis, a number of treatments may be attempted and specified according to the subtype of amyloidosis and the presence of complications. However, there are still significant challenges in treating this condition due to its complexity and lack of effective treatments. The prognosis for patients with cardiac amyloidosis is poor. Despite recent advances in diagnosis and treatment, there is still a need for more effective treatments to improve outcomes for patients with this condition. Therefore, we aim to review the current and future therapeutics reported in the literature and among ongoing clinical trials recruiting patients with CA.

Plastic or plastic-free life: From formation to removal.

Microplastics (MPs) and nanoplastics (NPs) have caused global environmental concerns due to their ubiquitous existence in our surrounding environment and the potential threats posed to the ecosystem and human health. This review aims to extend current knowledge on the formation and degradation of MPs and NPs. The paper presents the potential sources of MPs and NPs including plastic containers, textiles, cosmetics, personal care products, COVID-19 wastes, and other plastic products. Once in the natural environment, the fragmentation and degradation of plastic wastes are thought to be initiated by physical, chemical, and biological factors. The corresponding degradation mechanism will be presented in the present review. Given the plastic life and environment, humans are inevitably exposed to MPs and NPs through ingestion, inhalation, and dermal contact. The potential risks MPs/NPs pose to humans will be also discussed in our study. Currently, the relevance of MP/NP exposure to human health outcomes is still controversial and not yet fully understood. Deciphering the translocation and degradation of plastics in the human body will be helpful to reveal their potential organotoxicity. In this case, available approaches to alleviate MP/NP pollution and advanced strategies to reduce MP/NP toxicity in humans are recommended to build a plastic-free life.

Geometric Scaling of the Current-Phase Relation of Niobium Nanobridge Junctions.

The nanobridge junction (NBJ) is a type of Josephson junction that is advantageous for the miniaturization of superconducting circuits. However, the current-phase relation (CPR) of the NBJ usually deviates from a sinusoidal function, which has been explained by a simplified model with correlation only to its effective length. Here, we investigated both measured and calculated CPRs of niobium NBJs of a cuboidal shape with a three-dimensional bank structure. From a sine-wave to a sawtooth-like form, we showed that deviated CPRs of NBJs can be described quantitatively by its skewness Δθ. Furthermore, the measured dependence of Δθ on the critical current I0 from 108 NBJs turned out to be consistent with the calculated dependence derived from the change in geometric dimensions. This suggested that the CPRs of NBJs can be tuned by their geometric dimensions. In addition, the calculated scaling behavior of Δθ versus I0 in 3D space was provided for the future design of superconducting circuits of a high integration level by using niobium NBJs.

A novel 7α-hydroxysteroid dehydrogenase: Magnesium ion significantly enhances its activity and thermostability.

7α-Hydroxysteroid dehydrogenase (7α-HSDH) plays an important role in the efficient biotransformation of taurochenodeoxycholic acid (TCDCA) to tauroursodeoxycholic acid (TUDCA). In this paper, a novel NADP(H)-dependent 7α-HSDH (named J-1-1) was discovered, heterologously expressed in Escherichia coli and biochemically characterized. J-1-1 exhibited high enzymatic activities. The specific activities of J-1-1 toward TCDCA, glycochenodeoxycholic acid (GCDCA) and ethyl benzoylacetate (EBA) were 188.3 ± 0.2, 217.6 ± 0.4, and 20.0 ± 0.2 U·mg-1, respectively, in 50 mM Glycine-NaOH, pH 10.5. Simultaneously, J-1-1 showed high thermostability; 73% of its activity maintained after heat treatment at 40 °C for 100 h. Particularly noteworthy is that magnesium ion could stabilize the structure of J-1-1, resulting in the enhancement of its enzymatic activity and thermostability. The enzymatic activity of J-1-1 increased 40-fold in the presence of 50 mM Mg2+, and T0.5 increased by approximately 6 °C. Furthermore, after heat treatment at 40 °C for 20 min, the control group only retained 52% of the residual enzyme activity, while the residual enzyme activity of the experimental group was still 77% of the J-1-1 enzyme activity with Mg2+ and without heat treatment. These properties of 7α-HSDH would be expected to contribute to more extensive applications in the biotransformation of related substrates.

Observation of robust edge superconductivity in Fe(Se,Te) under strong magnetic perturbation.

The iron-chalcogenide high temperature superconductor Fe(Se,Te) (FST) has been reported to exhibit complex magnetic ordering and nontrivial band topology which may lead to novel superconducting phenomena. However, the recent studies have so far been largely concentrated on its band and spin structures while its mesoscopic electronic and magnetic response, crucial for future device applications, has not been explored experimentally. Here, we used scanning superconducting quantum interference device microscopy for its sensitivity to both local diamagnetic susceptibility and current distribution in order to image the superfluid density and supercurrent in FST. We found that in FST with 10% interstitial Fe, whose magnetic structure was heavily disrupted, bulk superconductivity was significantly suppressed whereas edge still preserved strong superconducting diamagnetism. The edge dominantly carried supercurrent despite of a very long magnetic penetration depth. The temperature dependences of the superfluid density and supercurrent distribution were distinctively different between the edge and the bulk. Our Heisenberg modeling showed that magnetic dopants stabilize anti-ferromagnetic spin correlation along the edge, which may contribute towards its robust superconductivity. Our observations hold implication for FST as potential platforms for topological quantum computation and superconducting spintronics.

Miniaturization of the Superconducting Memory Cell via a Three-Dimensional Nb Nano-superconducting Quantum Interference Device.

Scalable memories that can match the speeds of superconducting logic circuits have long been desired to enable a superconducting computer. A superconducting loop that includes a Josephson junction can store a flux quantum state in picoseconds. However, the requirement for the loop inductance to create a bistate hysteresis sets a limit on the minimal area occupied by a single memory cell. Here, we present a miniaturized superconducting memory cell based on a three-dimensional (3D) Nb nano-superconducting quantum interference device (nano-SQUID). The major cell area here fits within an 8 × 9 µm2 rectangle with a cross-selected function for memory implementation. The cell shows periodic tunable hysteresis between two neighboring flux quantum states produced by bias current sweeping because of the large modulation depth of the 3D nano-SQUID (∼66%). Furthermore, the measured current-phase relations (CPRs) of nano-SQUIDs are shown to be skewed from a sine function, as predicted by theoretical modeling. The skewness and the critical current of 3D nano-SQUIDs are linearly correlated. It is also found that the hysteresis loop size is in a linear scaling relationship with the CPR skewness using the statistics from characterization of 26 devices. We show that the CPR skewness range of π/4-3π/4 is equivalent to a large loop inductance in creating a stable bistate hysteresis for memory implementation. Therefore, the skewed CPR of 3D nano-SQUID enables further superconducting memory cell miniaturization by overcoming the inductance limitation of the loop area.

Structural and functional characterization of a novel acidophilic 7α-hydroxysteroid dehydrogenase.

7α-Hydroxysteroid dehydrogenase (7α-HSDH) is an NAD(P)H-dependent oxidoreductase belonging to the short-chain dehydrogenases/reductases. In vitro, 7α-HSDH is involved in the efficient biotransformation of taurochenodeoxycholic acid (TCDCA) to tauroursodeoxycholic acid (TUDCA). In this study, a gene encoding novel 7α-HSDH (named as St-2-1) from fecal samples of black bear was cloned and heterologously expressed in Escherichia coli. The protein has subunits of 28.3 kDa and a native size of 56.6 kDa, which suggested a homodimer. We studied the relevant properties of the enzyme, including the optimum pH, optimum temperature, thermal stability, activators, and inhibitors. Interestingly, the data showed that St-2-1 differs from the 7α-HSDHs reported in the literature, as it functions under acidic conditions. The enzyme displayed its optimal activity at pH 5.5 (TCDCA). The acidophilic nature of 7α-HSDH expands its application environment and the natural enzyme bank of HSDHs, providing a promising candidate enzyme for the biosynthesis of TUDCA or other related chemical entities.