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The concept of modular synthetic co-cultures holds considerable potential for biomanufacturing, primarily to reduce the metabolic burden of individual strains by sharing tasks among consortium members. However, current consortia often show unilateral relationships solely, without stabilizing feedback control mechanisms, and are grown in a shared cultivation setting. Such 'one pot' approaches hardly install optimum growth and production conditions for the individual partners. Hence, novel mutualistic, self-coordinating consortia are needed that are cultured under optimal growth and production conditions for each member. The heterologous production of the antibiotic violacein (VIO) in the mutually interacting E. coli–E. coli consortium serves as an example of this new principle. Interdependencies for growth control were implemented via auxotrophies for L-tryptophan and anthranilate (ANT) that were satisfied by the respective partner. Furthermore, VIO production was installed in the ANT auxotrophic strain. VIO production, however, requires low temperatures of 20–30 °C which conflicts with the optimum growth temperature of E. coli at 37 °C. Consequently, a two-compartment, two-temperature level setup was used, retaining the mutual interaction of the cells via the filter membrane-based exchange of medium. This configuration also provided the flexibility to perform individualized batch and fed-batch strategies for each co-culture member. We achieved maximum biomass-specific productivities of around 6 mg (g h)−1 at 25 °C which holds great promise for future applications. [ABSTRACT FROM AUTHOR]

The plague, caused by Yersinia pestis, is a natural focal disease and the presence of Y. pestis in the environment is a critical ecological concern worldwide. The role of Y. pestis phages in the ecological life cycle of the plague is crucial. Previously, a temperature-sensitive phage named vB_YpM_HQ103 was isolated from plague foci in Yunnan province, China. Upon infecting the EV76 strain of Y. pestis, vB_YpM_HQ103 exhibits lysogenic behavior at 21 °C and lytic behavior at 37 °C. Various methods including continuous passage lysogenic tests, in vitro lysis tests, comparative genomic assays, fluorescence quantitative PCR and receptor identification tests were employed to demonstrate that the lysogenic life cycle of this phage is applicable to wild Y. pestis strains; its lysogeny is pseudolysogenic (carrying but not integrating), allowing it to replicate and proliferate within Y. pestis. Furthermore, we have identified the outer membrane protein OmpA of Y. pestis as the receptor for phage infection. In conclusion, our research provides insight into the characteristics and receptors of a novel Y. pestis phage infection with a pseudolysogenic cycle. The findings of this study enhance our understanding of Y. pestis phages and plague microecology, offering valuable insights for future studies on the conservation and genetic evolution of Y. pestis in nature.

To improve the inventory management of cold chain logistics, we propose an economic order quantity (EOQ) inventory model for temperature-sensitive deteriorating products. Considering that the products are temperature-sensitive, the deterioration rate of the proposed model is a function of the temperature. In addition, the transportation cost, which is a function of the quantity ordered, is considered in this study. This article aims to find the optimal value of the total profit, selling price, and the length of the ordering cycle. Numerical examples are provided; the sensitivity analysis shows that the total profit is much more sensitive to transportation costs, compared with ordering and holding costs. [ABSTRACT FROM AUTHOR]

Currently, the marketed ophthalmic preparations of pranoprofen (PF) are mainly eye drops, but due to the special clearance mechanism of the eye and corneal reflex, the contact time between the drug and the focal site is short, most of the drug is lost, and the bioavailability is less than 5%. In the present study, an in situ gel eye drop containing no bacteriostatic agent and sensitive to temperature and ions was designed for delivery of PF. It was demonstrated to meet the criteria for ophthalmic preparations by characterization such as appearance content sterility. Ocular irritation tests showed a favorable safety profile. In vivo ocular retention time experiments showed that the ocular retention time of the pranoprofen gel was 4.41 times longer than that of commercially available drops (Pranopulin®), and the nasal tear excretion of the pranoprofen gel was lower than that of Pranopulin®, which suggests that the drug loss was reduced relative to that of the drops. The efficacy of the pranoprofen gel against tincture of cayenne pepper-induced corneal and conjunctival inflammation was examined using Pranopulin® as a control and in conjunction with inflammation scores, H&E slice results, and levels of IL-1β, IL-6, and TNF-α. The results showed that pranoprofen gel and Pranololin® had significant efficacy in the treatment of corneal and conjunctival inflammation, and the anti-inflammatory effect of pranoprofen gel was superior to that of Pranololin®. This study provides a new option for the treatment of corneal and conjunctival inflammation. [ABSTRACT FROM AUTHOR]

Flexible conductive sensor materials have received great attention for their sensitive electrical response to external conditions and their promising applications in flexible wearable and robotic applications. In this work, a highly stretchable force sensitive and temperature sensitive sensor material with a sandwich structure was prepared from the polydimethylsiloxane (PDMS) and the liquid metal (LM) gallium–indium–tin alloy (GaInSn). The sandwich structure (PDMS + PDMS/GaInSn + PDMS) was proven to prevent the "leakage" of LM. The preparation method of the sensing material was simple and time-saving (less than 1.5 h) and can be used for industrial production. The electrical performance analysis results confirmed that the resistance (R) of the material was sensitive to the external force, such as repeated stretching, compressing, bending, and impacting. The ΔR/R changed periodically and stably with the repeated stretching, when the GaInSn/Part A ≥ 0.4, the cyclic tensile strain ≤ 50%, and the cyclic tensile rate ≤ 2.5 mm/min. The R of the sensor materials was also responsive to the temperature, such as hot air and liquid nitrogen. In conclusion, this work provides a method for preparing sensing materials with the sandwich structure, which was confirmed to be sensitive to force and temperature without leaking LM, and it produced different types of R signals under different deformations and different temperatures. [ABSTRACT FROM AUTHOR]

Modern process research on phytoliths, including on the characteristics and spatial distribution of phytoliths assemblages and their relationship with environmental factors, is the basis of the use of phytoliths in paleoenvironmental reconstruction. We collected 54 surface soil samples along the isohyet of 600 mm in Northeast China in order to determine the relationship between modern phytoliths distributions and temperature. These were comprised by 20 samples from Xiaoxing'an Mountains, 32 samples from Songliao Plain, and 2 samples from Liaoxi Hills. The main phytoliths types were elongate and lanceolate, followed by short cell phytoliths, blocky, tabular and cuneiform; the percentages of the other types were all less than 1% and only occurred sporadically. There were significant differences in phytoliths assemblages among Xiaoxing'an Mountains, Songliao Plain, and Liaoxi Hills. Discriminant analysis was conducted using phytoiths assemblages, the samples from these three regions could be separated with a total accuracy of 96.30%. Elongate, lanceolate and pteridophyte‒type on average made up the largest proportion in Xiaoxing'an Mountains and the smallest in Liaoxi Hills, whereas saddle, bilobate and papillae showed the inverse trend; the proportions of blocky, tabular and cuneiform were the largest in Songliao Plain. The percentages of these types abovementioned were significantly different among the three regions. Correlation analysis revealed a significant negative correlation between the percentages of elongate, lanceolate and pteridophyte‒type and mean annual temperature (MAT), while there was a significant positive correlation between the percentages of blocky, tabular, cuneiform, saddle, bilobate, papillae and MAT. There was no significant relationship between rondel, trapeziform sinuate, conduit, carinate, sclereid, silicified stomata and MAT. A phytoliths index (C/W) based on the common phytoliths types in the surface soil samples which had a significant correlation with MAT was built. C/W = (elongate + lanceolate)/(elongate + lanceolate + blocky + tabular + cuneiform + saddle + bilobate). The values of C/W in Northeast China varied from 0.14 to 0.91, with an average of 0.67. The accuracy of the C/W index indicating climatic trends was significantly higher than the previously established Ic (climate index) and Iw (warm index). Overall, our results contribute to an improved understanding on the environmental significance of various phytoliths morphotypes, and provide a modern process foundation for phytoliths–based paleoclimatic reconstruction in the study region. [ABSTRACT FROM AUTHOR]

Active plasmonic nanostructures have attracted tremendous interest in nanophotonics and metamaterials owing to the dynamically switchable capabilities of plasmonic resonances. In this study, tunable hybrid plasmon resonances (HPR) of sodium metasurfaces through heat‐initiated structural transformation is experimentally demonstrated. A HPR is formed by coupling surface plasmon polaritons (SPP) and gap plasmon resonances (GPR), whose resonant wavelengths are highly sensitive to gaseous nanogaps. By carefully manipulating the thermo‐assisted spin‐coating process and post‐thermal treatment, tuning of the HPR is achieved because of the phase transition between the antidome and nanodome structural profiles of liquid sodium inside the patterned fused silica substrates. Furthermore, the figure of merit of the heat initiated variable structure‐spectrum is demonstrated that is highly dependent on the size of the substrate patterns, based on which temperature‐sensitive plasmonic color and "invisible ink" of sodium metasurfaces are demonstrated. These findings can lead to new solutions for manipulating low‐cost and high‐performance active plasmonic devices. [ABSTRACT FROM AUTHOR]

The control and regulation of thermal fields is of great significance in solving various thermal management problems in human life. Benefitting from the emerging space transformation technique and thermal meta-material, thermal meta-structures with unique thermal control capabilities have been rapidly developed in recent years. However, the exploration of the functional diversity of thermal meta-materials and structures is still inadequate; most related works are still limited to the single-field control effect and lack sensitivity to external environment changes. For the designed functional structures, observation and analysis of energy fluctuations and irreversible heat loss during the regulation process of the diffusive thermal field are also scare. Therefore, in this current work, we design a thermal meta-regulator (based on the space transformation theory) that is capable of differently distributing thermal energy according to the heat input direction and switching field control pattern with the change of ambient temperature. In addition to the common indicator of temperature, we also introduce the local entropy production rate and the total entropy production in the thermo-dynamic category to carry out entropy analysis of the energy processes involved in the thermal meta-regulator, making a multi-angle evaluation of the structural performance. Furthermore, we use the statistical response surface method to explore the comprehensive/interaction effect of multiple influencing factors on the thermal meta-regulator; the derived regression equations can be used to accurately predict the structural effects under different design schemes and temperature conditions. Our work further enriches the diversity and flexibility of thermal field manipulation manners and the demonstrated functions are also expected to be realized in other physical fields. [ABSTRACT FROM AUTHOR]

Bio-responsive polymers are the cornerstone of the creation of keen structures which, after getting unique stimuli like biotic indications as well as pathological irregularities, exhibit engineered biomedical functions. The creation of innovative products in precision medicine (a type of medicine that uses a person's own gene or protein knowledge to prevent, diagnose, or treat illness) has shown considerable promise in these stimulus-receptive schemes, and in recent years, there has been a lot of research on this topic. The goal of this analysis is to summaries the introductory consciousness and recent development of advanced bio-responsive technologies like in recent years, bio-responsive polymeric nanotherapeutics have emerged as an intriguing medium for safe and effective cancer treatment to promote tumor cell uptake and cause drug delivery at the target location. However, the bio-responsive polymer-based drug delivery system may suffer from drawbacks like the polymers may have safety issues and sometimes the stimuli fail to release the drugs incorporated into the systems resulting failure of the system. So, more research is needed to explore on the behavior of different bio-responsive polymers for development of strategic drug transport arrangement. In this article, we have focused on numerous bio-approachable polymers used for development of pH, temperature, magnetic field, light, sound responsive drug delivery system. Biological stimuli-sensitive polymeric drug delivery system [ABSTRACT FROM AUTHOR]

In this study, a temperature sensitive graft carbon dioxide‐based copolymer, poly (propylene oxide‐co‐carbon dioxide‐co‐allyl glycidyl ether)‐poly (N‐isopropylacrylamide)‐polyethylene glycol monomethyl ether (PPAG‐PNIPAm‐mPEG) was synthesized by "Click Chemistry". The hydrophobic main chain, PPAG, was prepared by the copolymerization of propylene oxide (PO) and allyl glycidyl ether (AGE). The branch chains include hydrophilic mPEG and temperature sensitive poly (N‐isopropylacrylamide). The structure of the polymer was characterized by 1H NMR and IR spectroscopy. Avermectin (AVE) was loaded into the nanoparticles to form PPAG‐PNIPAm‐mPEG@AVE nanoparticles. PPAG‐PNIPAm‐mPEG could self‐assemble into nano‐sized micelles in aqueous solution. And the size, zeta potential, critical micelle concentration (CMC) of PPAG‐PNIPAm‐mPEG nanoparticles can be altered by changing the lengths of the PNIPAm segments. The loading rate and encapsulation rate of PPAG‐PNIPAm‐mPEG@AVE were 36.98% and 89.98% respectively. The temperature sensitiveness of the nanomaterials was confirmed by DLS. The results show that temperature has a certain effect on the AVE release rate of PPAG‐PNIPAm‐mPEG@AVE in vitro. With the decrease of PNIPAm chain length, the AVE release rate decreases, and the contact angle of PPAG‐PNIPAm‐mPEG@AVE decreases compared with that of water. [ABSTRACT FROM AUTHOR]

To improve the inventory management of cold chain logistics, we propose an economic order quantity (EOQ) inventory model for temperature-sensitive deteriorating products. Considering that the products are temperature-sensitive, the deterioration rate of the proposed model is a function of the temperature. In addition, the transportation cost, which is a function of the quantity ordered, is considered in this study. This article aims to find the optimal value of the total profit, selling price, and the length of the ordering cycle. Numerical examples are provided; the sensitivity analysis shows that the total profit is much more sensitive to transportation costs, compared with ordering and holding costs.

Soil respiration (SR) is the second largest flux of carbon in most terrestrial ecosystems after photosynthesis. Research indicates that a slight change in climate conditions induces a variation of the SR that could be equal to the release of CO2 by fossil fuel emissions. For this reason, it is important to study what conditions control the variation of SR. Soil temperature is an important predictor of SR when there is no severe drought stress. The estimation of SR rates by the effect of temperature has been expressed with the Q10 relationship. This study aims to determine the Temperature Sensitivity (Q10) coefficient of the red-yellow soil organic carbon and estimate its conservation strategy using biochar. To analyze temperature sensitivity, each treatment was kept under 25°C and 35°C for 150 days, and the soil respiration ratio (SRR) as well as soil organic carbon (SOC) content were measured by the spectrophotometry method. Lastly, a treatment of biochar at 5% was added as a carbon conservation mechanism. The experimental results showed a significant difference in SOC content between different temperature conditions. After 150 days under treatment, 35°C treatment had a significant reduction of SOC in contrast with 25°C treatment (3.65 and 6.02 mg C/g respectively). The addition of biochar resulted in higher values of SOC at the same temperature, relative to non-biochar treatments. The Q10 value was higher in soil without biochar (1.82), while the addition of biochar reduces the coefficient to 1.12. The SRR was reduced gradually with higher values at 35°C, however, the biochar reduced the emission at 25°C lower than other treatments. The results indicated that the Q10 value of red-yellow soil can be affected by the addition of biochar, which works as a carbon source to maintain and increase SOC content and reduce the release of CO2 in the short term. [ABSTRACT FROM AUTHOR]

The environmental responsiveness of smart responsive gels under specific conditions has attracted great attention in recent years. In this paper, we have investigated the preparation of previously unreported electric field/temperature-sensitive three-dimensional graphene oxide hydrogels and their transdermal absorption studies, choosing indapamide (IND) as a model drug. Three-dimensional graphene oxide (3D@GO) has a unique three-dimensional network-like structure, excellent electrical properties, and mechanical properties. Three-dimensional graphene oxide network structures were prepared based on graphene oxide (GO) with the addition of formaldehyde, resorcinol, and sodium carbonate as reactants and catalysts. 3D@GO was compounded with a temperature-sensitive gel matrix, hydroxybutyl chitosan (HBC), to obtain a temperature-sensitive composite hydrogel with enhanced mechanical, electrical, and thermal properties. After applying 3D@GO–HBC to the skin, it can rapidly convert from liquid to semi-solid and adhere to the skin at the skin temperature. It can also be used as a carrier for controlled drug release under electric field conditions. This study of transdermal-controlled release drug delivery under electric field modulation showed that the cumulative release values of IND were 2.02 μg/cm2, 2.21 μg/cm2, 2.45 μg/cm2, 2.85 μg/cm2 , and 3.16 μg/cm2 in 24 h under the application of electric fields of 0 μA, 50 μA, 100 μA, 150 μA and 200 μA, respectively. The results indicated that 3D@GO–HBC hydrogels have good electrical sensitivity and can enhance the cumulative transdermal release of drugs under electric field conditions, providing an advantage not previously reported for controlled release of drugs. [ABSTRACT FROM AUTHOR]

Aminopeptidase I (Ape1) is one of the major cargoes of the cytoplasm‐to‐vacuole targeting (Cvt) pathway, which is a kind of selective autophagy, in Saccharomyces cerevisiae. After synthesis, the Ape1 precursor (prApe1) undergoes phase separation to form liquid droplets, termed Ape1 droplets, in the cytoplasm. In this study, we found that cells expressing prApe1‐GFP exhibited temperature‐sensitive formation of Ape1 droplets, which affected its transport. Moreover, we showed that endogenous Ape1 transport was defective at high temperatures in various laboratory strains due to the defect in the formation of Ape1 droplets at these temperatures. Finally, we found that gene disruptants showing heat‐tolerant growth suppressed the temperature sensitivity of the Ape1 transport. The formation of Ape1 droplets might be an indicator of cytoplasmic integrity at high temperature. [ABSTRACT FROM AUTHOR]

• A new Y. pestis phage was isolated and identified. • we identified a pseudolysogenic Y. pestis phage. The phage existed as a plasmid-like at 21 °C and could enter the lytic cycle to release offspring when the temperature increased to 37 °C. • we discovered that the outer membrane protein OmpA on the surface of Y. pestis is one of the receptors for phage HQ103. The plague, caused by Yersinia pestis , is a natural focal disease and the presence of Y. pestis in the environment is a critical ecological concern worldwide. The role of Y. pestis phages in the ecological life cycle of the plague is crucial. Previously, a temperature-sensitive phage named vB_YpM_HQ103 was isolated from plague foci in Yunnan province, China. Upon infecting the EV76 strain of Y. pestis , vB_YpM_HQ103 exhibits lysogenic behavior at 21 °C and lytic behavior at 37 °C. Various methods including continuous passage lysogenic tests, in vitro lysis tests, comparative genomic assays, fluorescence quantitative PCR and receptor identification tests were employed to demonstrate that the lysogenic life cycle of this phage is applicable to wild Y. pestis strains; its lysogeny is pseudolysogenic (carrying but not integrating), allowing it to replicate and proliferate within Y. pestis. Furthermore, we have identified the outer membrane protein OmpA of Y. pestis as the receptor for phage infection. In conclusion, our research provides insight into the characteristics and receptors of a novel Y. pestis phage infection with a pseudolysogenic cycle. The findings of this study enhance our understanding of Y. pestis phages and plague microecology, offering valuable insights for future studies on the conservation and genetic evolution of Y. pestis in nature. [ABSTRACT FROM AUTHOR]

Flexible conductive sensor materials have received great attention for their sensitive electrical response to external conditions and their promising applications in flexible wearable and robotic applications. In this work, a highly stretchable force sensitive and temperature sensitive sensor material with a sandwich structure was prepared from the polydimethylsiloxane (PDMS) and the liquid metal (LM) gallium–indium–tin alloy (GaInSn). The sandwich structure (PDMS + PDMS/GaInSn + PDMS) was proven to prevent the “leakage” of LM. The preparation method of the sensing material was simple and time-saving (less than 1.5 h) and can be used for industrial production. The electrical performance analysis results confirmed that the resistance (R) of the material was sensitive to the external force, such as repeated stretching, compressing, bending, and impacting. The ΔR/R changed periodically and stably with the repeated stretching, when the GaInSn/Part A ≥ 0.4, the cyclic tensile strain ≤ 50%, and the cyclic tensile rate ≤ 2.5 mm/min. The R of the sensor materials was also responsive to the temperature, such as hot air and liquid nitrogen. In conclusion, this work provides a method for preparing sensing materials with the sandwich structure, which was confirmed to be sensitive to force and temperature without leaking LM, and it produced different types of R signals under different deformations and different temperatures.

The control and regulation of thermal fields is of great significance in solving various thermal management problems in human life. Benefitting from the emerging space transformation technique and thermal meta-material, thermal meta-structures with unique thermal control capabilities have been rapidly developed in recent years. However, the exploration of the functional diversity of thermal meta-materials and structures is still inadequate; most related works are still limited to the single-field control effect and lack sensitivity to external environment changes. For the designed functional structures, observation and analysis of energy fluctuations and irreversible heat loss during the regulation process of the diffusive thermal field are also scare. Therefore, in this current work, we design a thermal meta-regulator (based on the space transformation theory) that is capable of differently distributing thermal energy according to the heat input direction and switching field control pattern with the change of ambient temperature. In addition to the common indicator of temperature, we also introduce the local entropy production rate and the total entropy production in the thermo-dynamic category to carry out entropy analysis of the energy processes involved in the thermal meta-regulator, making a multi-angle evaluation of the structural performance. Furthermore, we use the statistical response surface method to explore the comprehensive/interaction effect of multiple influencing factors on the thermal meta-regulator; the derived regression equations can be used to accurately predict the structural effects under different design schemes and temperature conditions. Our work further enriches the diversity and flexibility of thermal field manipulation manners and the demonstrated functions are also expected to be realized in other physical fields.

Temperature‐sensitive nanocapsules with controllable release properties were synthesized through miniemulsion free radical polymerization method. Temperature‐sensitive N,N‐diethylacrylamide/N,N‐dimethylacrylamide (DEA/DMA) copolymer were systematically synthesized as shell materials, and the fragrance‐dementholized peppermint oil (DPO) was encapsulated as hydrophobic core material. The as prepared nanocapsules had high encapsulation efficiencies of more than 90% and small average diameters of less than 150 nm, as well as narrow polydispersity index (PDI) below 0.17. Furthermore, decreased DEA contents in shell material resulted in higher phase transition temperature and slower release rate of fragrance under the same temperature. By varying the copolymer composition of shell materials, the controllable release property of as prepared nanocapsules were also varied under different temperatures. [ABSTRACT FROM AUTHOR]

Purpose: In the pharmaceutical industry, there has been a growing interest in continuous manufacturing in recent years. Many efforts have been made to implement new process equipment for various production steps. One step which is not yet covered well is the continuous drying of the active pharmaceutical ingredient (API) after it has been crystallized with the desired particle properties. The dryer prototype, developed in this study, can operate continuously with poorly flowable materials. Methods: After initial testing of a paddle dryer, an optimized prototype was designed and built. Ibuprofen and di-calcium phosphate were used as test substances. Ibuprofen was used because of its bad processability due to poor flowability and very low melting point. This makes it well-suited for simulating other APIs as a worst case. Di-calcium phosphate has a very good flow behavior and represents the other extreme of the plausible flow properties. Results: In the paddle dryer, significant accumulation led to an unstable residence time distribution (RTD). Hence, the dryer was unsuitable for non-ideal pharmaceutical products. However, the product properties were very promising (i.e., little to no attrition and almost no agglomeration, as well as dry product); therefore, a new dryer design was developed. As a result, the undesired accumulation of material in the dryer was significantly reduced. The introduction of a gentle, forced flow improved the RTD, and it was possible to run the dryer continuously for extended periods of time (5.5 h), with a stable holdup. Conclusion: The optimized flow of powder within the newly developed dryer does not only enable continuous drying but also reduces the drying time (in comparison with batch) and guarantees that the individual particle is dried without change. Further work with different materials and process conditions should follow, to evaluate the applicability of the dryer as sustainable technology. [ABSTRACT FROM AUTHOR]

The p53 tumor suppressor is inactivated by mutations in about 50% of tumors. Rescuing the transcriptional function of mutant p53 has potential therapeutic benefits. Approximately 15% of p53 mutants are temperature sensitive (TS) and regain maximal activity at 32°C. Proof of concept study showed that induction of 32°C hypothermia in mice restored TS mutant p53 activity and inhibited tumor growth. However, 32°C is the lower limit of therapeutic hypothermia procedures for humans. Higher temperatures are preferable but result in suboptimal TS p53 activation. Recently, arsenic trioxide (ATO) was shown to rescue the conformation of p53 structural mutants by stabilizing the DNA binding domain. We examined the responses of 17 frequently observed p53 TS mutants to functional rescue by temperature shift and ATO. The results showed that ATO only rescued mild p53 TS mutants with high basal activity at 37°C. Mild TS mutants showed a common feature of regaining significant activity at the semi-permissive temperature of 35°C and could be further stimulated by ATO at 35°C. TS p53 rescue by ATO was antagonized by the cellular redox mechanism and was rapidly reversible. Inhibition of glutathione (GSH) biosynthesis enhanced ATO rescue efficiency and sustained p53 activity after ATO washout. The results suggest that mild TS p53 mutants are uniquely responsive to functional rescue by ATO due to small thermostability deficits and inherent potential to regain active conformation. Combining mild hypothermia and ATO may provide an effective and safe procedure for targeting tumors with p53 TS mutations., (© 2024 Wiley Periodicals LLC.)

The progress of nanotechnology enables us to make use of the special properties of materials on the nanoscale and open up many new fields of biomedical research. Among them, thermosensitive nanomaterials stand out in many biomedical fields because of their “intelligent” behavior in response to temperature changes. However, this article mainly reviews the research progress of thermosensitive nanomaterials, which are popular in biomedical applications in recent years. Here, we simply classify the thermally responsive nanomaterials according to the types of polymers, focusing on the mechanisms of action and their advantages and potential. Finally, we deeply investigate the applications of thermosensitive nanomaterials in drug delivery, tissue engineering, sensing analysis, cell culture, 3D printing, and other fields and probe the current challenges and future development prospects of thermosensitive nanomaterials.

The novel pH and thermo-sensitive amphiphilic triblock copolymer poly(methyl methacrylate)-block-poly(N-isopropylacrylamide)-block-poly[N,N-(dimethylamino) ethyl methacrylate] (PMMA-b-PNIPAM-b-PDMAEMA) was synthesized by ATRP. We have prepared the AB amphiphilic copolymer (PMMA-b-PNIPAM) and ABC amphiphilic triblock copolymer (PMMA-b-PNIPAM-b-PDMAEMA) of expected molecular mass. It was characterized by GPC,1HNMR and FT-IR spectroscopy. The AB amphiphilic copolymer ability of temperature response and the morphology of self-assembly micelles different in toluene, THF, and DMF. ABC amphiphilic triblock copolymer self-assembled petal structure in alkaline aqueous solution, and lamellar structure in acidic aqueous solution. Moreover, the transmittance of micellar solution changes with the increase of temperature; these changes reflect the pH and thermo-sensitivity of the block copolymer. The micelles behavior and morphology of the system were studied by transmission electron microscopy (TEM) and dynamic light scattering (DLS). [ABSTRACT FROM AUTHOR]

In our study, as a functional monomer, p-(methacryloyloxy)acetanilide (MOAA) was synthesized and utility in hydrogel systems with various commercial monomers after the structural characterization was analyzed. In terms of temperature sensitivity and suitability for use in biological applications, N-isopropyl acrylamide (NIPAm) monomer and pH-sensitive acrylic acid (AAc) monomer were chosen among the commercial monomers. To the best of our knowledge, p(N-isopropyl acrylamide-co-p-(p-methacryloyloxy)acetanilide) (GEL 5) and p(N-isopropyl acrylamide-co-acrylic acid-co-p-(p-methacryloyloxy)acetanilide) (GEL 8) were synthesized in the form of a film with the free radical polymerization technique for first time in the literature. The structural characterizations and surface morphologies of the hydrogels p(NIPAm) (GEL 1), p(NIPAm-co-MOAA) (GEL 5), and p(NIPAm-co-AAc-co-MOAA) (GEL 8) were investigated by using the techniques of FTIR spectroscopy and scanning electron microscope (SEM). Moreover, the thermal resistance of all three hydrogels was brightened by the thermal gravimetric analysis (TGA). Swelling behaviors in different environments of the MOAA-based hydrogels, prepared as pH and temperature-sensitive, were examined, and biomedical applications are occurred by the investigation of the usability as a controlled drug delivery material. For this purpose, sodium diclofenac (NaDc) drug, used in pain and inflammation treatment, was chosen. In vitro release of NaDc from the drug-loaded hydrogel was examined in pH 5.5 (PBS) and pH 7.4 (PBS) media. Korsmeyer-Peppas model was used in defining the drug release mechanism. [ABSTRACT FROM AUTHOR]

ABSTRACT Influenza A viruses (IAV) remain emerging threats to human public health. Live-attenuated influenza vaccines (LAIV) are one of the most effective prophylactic options to prevent disease caused by influenza infections. However, licensed LAIV remain restricted for use in 2- to 49-year-old healthy and nonpregnant people. Therefore, development of LAIV with increased safety, immunogenicity, and protective efficacy is highly desired. The U.S.-licensed LAIV is based on the master donor virus (MDV) A/Ann Arbor/6/60 H2N2 backbone, which was generated by adaptation of the virus to growth at low temperatures. Introducing the genetic signature of the U.S. MDV into the backbone of other IAV strains resulted in varying levels of attenuation. While the U.S. MDV mutations conferred an attenuated phenotype to other IAV strains, the same amino acid changes did not significantly attenuate the pandemic A/California/04/09 H1N1 (pH1N1) strain. To attenuate pH1N1, we replaced the conserved leucine at position 319 with glutamine (L319Q) in PB1 and analyzed the in vitro and in vivo properties of pH1N1 viruses containing either PB1 L319Q alone or in combination with the U.S. MDV mutations using two animal models of influenza infection and transmission, ferrets and guinea pigs. Our results demonstrated that L319Q substitution in the pH1N1 PB1 alone or in combination with the mutations of the U.S. MDV resulted in reduced pathogenicity (ferrets) and transmission (guinea pigs), and an enhanced temperature sensitive phenotype. These results demonstrate the feasibility of generating an attenuated MDV based on the backbone of a contemporary pH1N1 IAV strain. IMPORTANCE Vaccination represents the most effective strategy to reduce the impact of seasonal IAV infections. Although LAIV are superior in inducing protection and sterilizing immunity, they are not recommended for many individuals who are at high risk for severe disease. Thus, development of safer and more effective LAIV are needed. A concern with the current MDV used to generate the U.S.-licensed LAIV is that it is based on a virus isolated in 1960. Moreover, mutations that confer the temperature-sensitive, cold-adapted, and attenuated phenotype of the U.S. MDV resulted in low level of attenuation in the contemporary pandemic A/California/04/09 H1N1 (pH1N1). Here, we show that introduction of PB1 L319Q substitution, alone or in combination with the U.S. MDV mutations, resulted in pH1N1 attenuation. These findings support the development of a novel LAIV MDV based on a contemporary pH1N1 strain as a medical countermeasure against currently circulating H1N1 IAV.

We synthesized a temperature-sensitive antibacterial hydrogel, defined as NIPAM-CG/GM hydrogel. First, vinyl carboxymethyl chitosan (CG) was synthesized as a crosslinking carrier and silane dispersed graphene (GM) was synthesized as a reinforcer. Then, the N-isopropylacrylamide (NIPAM) monomer was free-radical polymerized with the vinyl groups of CG and GM to form a NIPAM-CG/GM hydrogel without any crosslinking agent. The influences of different hydrogel compositions on the microstructure, compressive properties, swelling, drug loading, and drug release properties of the hydrogels were discussed, and its temperature sensitivity was also demonstrated. The results showed that the lower critical solution temperature (LCST) and mechanical properties of the hydrogel could be adjusted by controlling the amount of CG and GM. Next, its biocompatibility was characterized, and its antibacterial performance was tested against Escherichia coli and Staphylococcus aureus. The antibacterial mechanism was explained by measuring the difference in the ion concentration outside the membrane and changes in the morphology of live/dead bacteria. NIPAM-CG/GM had a high drug loading and nearly complete drug release at a physiological temperature of 37 °C. Its moderate mechanical properties, excellent biocompatibility, and antibacterial effects give NIPAM-CG/GM great potential applications as a wound dressing. [Display omitted] • Highly-stable and dispersed silanized graphene was prepared • Vinyl groups were introduced into carboxymethyl chitosan as a carrier for free-radical polymerization • The introduction of inorganic nanoparticles enhanced the mechanical properties of the hydrogel • Free radical polymerization of NIPAM made the hydrogel temperature-responsive • NIPAM-CG/GM hydrogel displayed excellent antibacterial activity and biocompatibility [ABSTRACT FROM AUTHOR]

Chloroplasts are indispensable for higher plants. The growth and development of plants are very sensitive to environmental temperature changes, and chloroplast development is also regulated by adverse environmental temperatures. However, the molecular mechanism of how plants coordinate chloroplast development and environmental temperature changes remains largely unknown. Here, a temperature-conditioned chloroplast development defective mutant t hermo- s ensitive mutant in l eaf color 2 (tsl2) of Arabidopsis was obtained through a forward genetic screening. The tsl2 mutant showed a weak yellowish phenotype at normal growth temperature (22°C), and the phenotype was more pronounced at low growth temperature (16°C) and largely rescued at high growth temperature (29°C). Bulk Segregant Analysis (BSA) revealed that TSL2 encodes FtsH-Inactive Protein 5 (FtsHi5). Genetic complementation analysis confirmed that complemented expression of FtsHi5 rescued the chlorophyll content and thylakoid development defects observed in tsl2 mutants at 16°C. Quantitative mass spectrometry analysis with Tandem Mass Tag (TMT) isobaric labeling revealed broad changes in the chloroplast proteome of tsl2 mutant plants at low temperature, which is agreed with the impaired chloroplast biogenesis and function in tsl2 plants. Together, our data demonstrates that FtsHi5/TSL2 plays an important role in chloroplast development and protein accumulation in chloroplasts, especially at low environmental temperatures in Arabidopsis. [ABSTRACT FROM AUTHOR]

The temperature sensitive copolymer of microsize hydrogels consist of N-isopropylacrylamide (NIPAM) and 2- acrylamido-2 methylpropanesulphonic acid (AMPS) have been synthesized by soap free emulsion polymerization method in the presence of polyethylene glycol (PEG) as macro initiator and N, N´-methylenebisacrylamide (NMBA) as crosslinker. In this work, Dynamic Light Scattering (DLS), Transmission Electron Microscope (TEM) and Atomic Force Microscope (AFM) technique were used for structural analysis of microgels. It was found that particle size observed by TEM and AFM were spherical with a diameter around 103.0 nm to 133.1 nm and 121.1 nm to 189.0 nm. While DLS measurement shows narrow particle size distribution with hydrodynamic diameter from 343.6nm to 528 nm at a temperature 25°C and 132.5nm to 414.4nm at temperature 50°C depending on the AMPS content in Microgels samples. The surface roughnesses of particles were observed to be increasing with increased AMPS content. Moreover, decrease in hydrodynamic diameter from 25°C to 50°C revealed the temperature sensitivityproperty of microgels. [ABSTRACT FROM AUTHOR]

Chloroplasts are indispensable for higher plants. The growth and development of plants are very sensitive to environmental temperature changes, and chloroplast development is also regulated by adverse environmental temperatures. However, the molecular mechanism of how plants coordinate chloroplast development and environmental temperature changes remains largely unknown. Here, a temperature-conditioned chloroplast development defective mutant thermo-sensitive mutant in leaf color 2 (tsl2) of Arabidopsis was obtained through a forward genetic screening. The tsl2 mutant showed a weak yellowish phenotype at normal growth temperature (22°C), and the phenotype was more pronounced at low growth temperature (16°C) and largely rescued at high growth temperature (29°C). Bulk Segregant Analysis (BSA) revealed that TSL2 encodes FtsH-Inactive Protein 5 (FtsHi5). Genetic complementation analysis confirmed that complemented expression of FtsHi5 rescued the chlorophyll content and thylakoid development defects observed in tsl2 mutants at 16°C. Quantitative mass spectrometry analysis with Tandem Mass Tag (TMT) isobaric labeling revealed broad changes in the chloroplast proteome of tsl2 mutant plants at low temperature, which is agreed with the impaired chloroplast biogenesis and function in tsl2 plants. Together, our data demonstrates that FtsHi5/TSL2 plays an important role in chloroplast development and protein accumulation in chloroplasts, especially at low environmental temperatures in Arabidopsis.

Soil organic carbon (SOC) has an important role as a key indicator for soil health due to its contributions on mitigation and adaptation to climate change. Tropical areas cover with Red-yellow soil (Udults) such as Amazon represents the highest amount of soil carbon sources in the earth. Although it is affected by human impacts due to deforestation, it is important to maintain and increase SOC of tropical Red-yellow soil toward an optimal level for meeting challenges such as mitigating climate change effects. The aim of this study is to analyze the stabilization of soil organic carbon from Red-yellow soil under different temperatures conditions. A detailed comparison was made between forested and deforested conditions of Red-yellow soil. In order to analyze the temperature sensitivity, each treatment was kept under 25℃ and 35℃, and the soil respiration ratio (SRR) was measured as well as SOC content by spectrophotometry method. Lastly, a treatment of biochar at 5% was added as part of stabilization mechanisms of carbon. The experimental results showed that there were significant differences in SOC content between forested conditions in contrast to deforested conditions, where 7.25 mg C/g was found in forest conditions while deforested conditions was 5.68 mg C/g. Although it was not found significant change in SOC under different temperature, SRR increased at 39% from 8.87 μL CO2/h/g to 11.90 μL CO2/h/g with temperature changes from 25℃ to 35℃. Additionally, biochar application contributes to increase the value of SOC at more than 2.66 mg C/g in all treatments, however, it did not make a significant difference in SRR by temperature changes. Thus, biochar works as carbon sources to maintain and increase SOC content, but stabilization effects on Soil Respiration Ratio (SRR) should be observed in long term. [ABSTRACT FROM AUTHOR]

Phase change materials (PCMs) with large latent heat capacity and efficient thermal response have great potential for thermal management in various applications. Uniform phase change composite beads were fabricated based on phase change medium 1-tetradecanol (TD) as gatekeeper and core-satellites zinc oxide @ poly(N-isopropyl acrylamide) (ZnO@PNIPAM) using a simple injection device at 50 ℃. It was demonstrated that the ZnO@PNIPAM/TD PCM system possessed a high latent heat value of 230 J g−1. The ZnO nanospheres acted as the core and the phase change material TD was the shell. Furthermore, the satellites PNIPAM nanoparticles acted as a reservoir. The enthalpy values of ZnO@PNIPAM/TD kept high (233.04 J g−1 and 229.41 J g−1) compared with pure TD. The suitable melting temperature of the temperature sensitive PCM is about 38.5 ℃ close to the human body temperature. The unique core-satellites structure of the system can store small molecules, which not only has its own excellent characteristics but also can give the system rich functionality.

Objective: To investigate the clinical course and genetic etiology of familial temperature-sensitive auditory neuropathy (TSAN), which is a very rare subtype of auditory neuropathy (AN) that involves an elevation of hearing thresholds due to an increase in the core body temperature, and to evaluate the genotype–phenotype correlations in a family with TSAN.Methods: Six members of a non-consanguineous Chinese family, including four siblings complaining of communication difficulties when febrile, were enrolled in this study. The clinical and audiological profiles of the four siblings were fully evaluated during both febrile and afebrile episodes, and the genetic etiology of hearing loss (HL) was explored using next-generation sequencing (NGS) technology. Their parents, who had no complaints of fluctuating HL due to body temperature variation, were enrolled for the genetics portion only.Results: Audiological tests during the patients’ febrile episodes met the classical diagnostic criteria for AN, including mild HL, poor speech discrimination, preserved cochlear microphonics (CMs), and absent auditory brainstem responses (ABRs). Importantly, unlike the pattern observed in previously reported cases of TSAN, the ABRs and electrocochleography (ECochG) signals of our patients improved to normal during afebrile periods. Genetic analysis identified a compound heterozygous variant of the OTOF gene (which encodes the otoferlin protein), including one previously reported pathogenic variant, c.5098G > C (p.Glu1700Gln), and one novel variant, c.4882C > A (p.Pro1628Thr). Neither of the identified variants affected the C2 domains related to the main function of otoferlin. Both variants faithfully cosegregated with TSAN within the pedigree, suggesting that OTOF is the causative gene of the autosomal recessive trait segregation in this family.Conclusion: The presence of CMs with absent (or markedly abnormal) ABRs is a reliable criterion for diagnosing AN. The severity of the phenotype caused by dysfunctional neurotransmitter release in TSAN may reflect variants that alter the C2 domains of otoferlin. The observations from this study enrich the current understanding of the phenotype and genotype of TSAN and may lay a foundation for further research on its pathogenesis.

[Display omitted] Wound dressings are used to promote wound healing, but by using traditional dressings, scars are easily left at the site of the wound. Inspired by the recovery of scarring in embryonic wounds, various mechanoactive wound dressings have attracted the attention of scientists. Among them, Poly (N-isopropyl acrylamide) (PNIPAM) based hydrogels are more suitable for humans since their phase transition temperature is close to the surface temperature of the human body. It makes it easy to produce mechanical forces by giving external stimuli. In addition, PNIPAM-based hydrogels have excellent mechanical properties and strong adhesive strength for use in mechanical wound dressings. Numerous types of mechanoactive wound dressings made from PNIPAM-based hydrogels have emerged in the last decade, including biomechanically active wound dressings, peelable mechanical wound dressings, and double-layer mechanical wound dressings. Therefore, in this work, a summary of mechanoactive wound dressings made by PNIPAM-based hydrogels is presented to provide researchers with a clear understanding of these emerging mechanoactive wound dressings. [ABSTRACT FROM AUTHOR]

Generally, the conventional rejuvenator contains many mineral oils to supply the missing components of aged bitumen. The mineral oils could recover the performance of aged bitumen go through a long-term aging process. However, the mineral oils are easy to volatilize at higher recycling temperature. The higher volatilization will reduce the effect of rejuvenator and limit proportion of reclaimed asphalt pavement (RAP) in recycled asphalt mixture (RAP contents less than 30%). The main components of vegetable oil are straight chain higher fatty acids and glycerides. The esters of straight chain higher fatty acids and glycerol are not volatile at high temperature. Therefore, they can be used to recover the micro chemical composition of bitumen and a change in colloidal stability of asphaltene. In this research, two newly kinds of bitumen rejuvenator were developed by replacing mineral oil with waste cooking corn and soybean oil. The two kinds of vegetable and a mineral bitumen rejuvenators were utilized to recover aged bitumen with 2–10% by weigh. The objectives of the research are evaluating the rheological properties, high temperature and fatigue performance of the recovered bitumen. The Dynamic Shear Rheometer Test and Rotational Viscosity Test were conducted according to the AASHTO and ASTM standards. Additionally, the crack resistance of bitumen was evaluated by using the bending beam rheometer (BBR) test at −12 and −18°C. The result of laboratory test and statistical analysis of ANOVA showed that the vegetable oil rejuvenators effectively reduce the viscosity and stiffness of aged bitumen. It will improve both the fatigue resistance and low temperature crack resistance. In addition, when the content of vegetable oil is higher, the rejuvenating agent can make the recovered bitumen have lower viscosity and stiffness. Considering that the rutting resistance under high temperature, it is suggested that 6 and 8% vegetable oil be used to recover the aged bitumen.

Linear diepoxide-terminated poly(ethylene glycol) (PEG) of molar mass 600, 1000 and 2000 g mol−1 was end-linked with dendrimer-star polymer (PAMAM) of generations 1.0 in water to prepare architecturally well-defined copolymer hydrogels. The structures and properties of the products were characterized using infrared, 1H NMR, DSC measurements, scanning electron microscopy (SEM) and swelling behavior tests. The swelling behavior of these hydrogels was tested in distilled water at constant temperature and the equilibrium swelling ratio (ESR) was determined for structurally different hydrogels and various environmental conditions, which showed that ESR was influenced by the molecular weight of PEG, the molar ratio of H amine groups/epoxy groups, temperature and pH. Higher ESR was obtained for either longer-chain PEG, non-stoichiometric H amine/epoxy groups ratio, acidic pH or lower temperatures. When the hydrogel was switched from 10 °C to 65 °C and pH 3.5 to 11.5, the swelling behavior of the hydrogels showed good reversibility for swelling–deswelling. When the molecular weight of PEG was changed in the range of 600–2000, the lower critical solution temperature (LCST) of hydrogel increased from 30 to 40 °C. When the molar ratio of H amine/epoxy groups was changed, the LCST was not significantly changed. [ABSTRACT FROM AUTHOR]

Chlorophyll (Chl) is an essential molecule for harvesting light energy in photosynthetic organisms. We isolated yellow leaf 3 (yl3), a rice Chl-deficient mutant, which showed yellow leaves with decreased Chl content and abnormal chloroplast development. Positional cloning revealed that YL3 encodes OsCHLH, a subunit of magnesium-chelatase. In yl3, one amino acid substitution occurs at the C-terminal region of a highly conserved amino acid residue. YL3 is constitutively expressed in all tissues. Compared with the wild type, yl3 was found to be sensitive to low temperature. The expression levels of genes for Chl biosynthesis, photosynthesis and chloroplast development were strongly reduced in yl3. These results provide novel insights regarding how rice chloroplast development and Chl synthesis are regulated by YL3. [ABSTRACT FROM AUTHOR]

Rehman M, Ihsan A, Madni A, et al. Int J Nanomedicine. 2021;16:5187. The authors have advised Figure 3 on page 5187 is incorrect. An error was made in the labelling of the scale bar for figure part 3B. The correct Figure 3 is shown in Download Article. The authors apologize for this error. Read the original articlePrevious corrigendum has been published

Magnetic and temperature-sensitive solid lipid particles (mag. SLPs) were prepared in the presence of oleic acid-coated iron oxide (IO-OA) nanoparticles with 1-tetradecanol and poly(ethylene oxide)-block-poly(ε-caprolactone) as lipid and stabilizing surfactant-like agents, respectively. The particles, typically ~850 nm in hydrodynamic size, showed heat dissipation under the applied alternating magnetic field. Cytotoxic activity of the mag.SLPs, non-magnetic SLPs, and iron oxide nanoparticles was compared concerning the mammalian cancer cell lines and their drug-resistant counterparts using trypan blue exclusion test and MTT assay. The mag.SLPs exhibited dose-dependent cytotoxicity against human leukemia cell lines growing in suspension (Jurkat and HL-60/wt), as well as the doxorubicin (Dox)- and vincristine-resistant HL-60 sublines. The mag.SLPs showed higher cytotoxicity toward drug-resistant sublines as compared to Dox. The human glioblastoma cell line U251 growing in a monolayer culture was also sensitive to mag.SLPs cytotoxicity. Staining of U251 cells with the fluorescent dyes Hoechst 33342 and propidium iodide (PI) revealed that mag.SLPs treatment resulted in an increased number of cells with condensed chromatin and/or fragmented nuclei as well as with blebbing of the plasma membranes. While the Hoechst 33342 staining of cell suggested the pro-apoptotic activity of the particles, the PI staining indicated the pro-necrotic changes in the target cells. These conclusions were confirmed by Western blot analysis of apoptosis-related proteins, study of DNA fragmentation (DNA laddering due to the inter-nucleosomal cleavage and DNA comets due to single strand breaks), as well as by FACS analysis of the patterns of cell cycle distribution (pre-G1 phase) and Annexin V/PI staining of the treated Jurkat cells. The induction of apoptosis or necrosis by the particles used to treat Jurkat cells depended on the dose of the particles. Production of the reactive oxygen species (ROS) was proposed as a potential mechanism of mag.SLPs-induced cytotoxicity. Accordingly, hydrogen peroxide and superoxide radical levels in mag.SLPs-treated Jurkat leukemic cells were increased by ~20–40 and ~70%, respectively. In contrast, the non-magnetic SLPs and neat iron oxides did not influence ROS levels significantly. Thus, the developed mag.SLPs can be used for effective killing of human tumor cells, including drug-resistant ones.

Hydrogels are among the most used polymer–drug systems, polysaccharide-based materials presenting many advantages to be used for controlled release applications. Gellan maleate/NIPAm hydrogels are hydrophilic swelling matrixes that were originally developed for biomedical applications as controlled release dosage forms. The purpose of this study is to explore the ability of gellan maleate/NIPAm thermoreversible hydrogels for ophthalmic applications as ocular inserts. Studied hydrogels were synthesized by free radical grafting/polymerization of unsaturated esters (gellan maleate) with N-isopropylacrylamide (NIPAm) and N,N′-methylenebisacrylamide as cross-linker. They are evaluated for swelling degree, in vitro inclusion and release of drugs (adrenaline and chloramphenicol) and in vivo biocompatibility. The hydrogel is shown to be a temperature-responsive material with a LCST close to 36 °C. The swelling properties and the release of biologically active compounds occur when polymer conformation changes determining phase transition at LCST. Gellan-based hydrogels present reproducible responses to alternation between ambient temperature and human body one. The stability and biocompatibility were evaluated in vitro and in vivo. Tissue response to implantation of hydrogel was determined by histological analysis (haematoxylin–eosin–methylene blue and periodic acid–Schiff). A thin fibrous capsule was observed around the implanted hydrogels. No necrosis, calcification and acute inflammatory reaction were noted. Successful preliminary results were obtained for ophthalmic applications. [ABSTRACT FROM AUTHOR]

Mubashar Rehman,1–3 Ayesha Ihsan,2 Asadullah Madni,1 Sadia Zafar Bajwa,2 Di Shi,3 Thomas J Webster,3,4 Waheed S Khan2 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Punjab, Pakistan; 2Nanobiotech Group, National Institute of Biotechnology and Genetic Engineering, Faisalabad, Punjab, Pakistan; 3Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 4Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Thermoresponsive drug delivery systems are designed for the controlled and targeted release of therapeutic payload. These systems exploit hyperthermic tempera­tures (>39°C), which may be applied by some external means or due to an encountered symptom in inflammatory diseases such as cancer and arthritis. The objective of this paper was to provide some solid evidence in support of the hypothesis that solid lipid nanoparticles (SLNs) can be used for thermoresponsive targeting by undergoing solid–liquid phase transition at their melting point (MP). Thermoresponsive lipid mixtures were prepared by mixing solid and liquid natural fatty acids, and their MP was measured by differential scanning calorimetry (DSC). SLNs (MP 39°C) containing 5-fluorouracil (5-FU) were synthesized by hot melt encapsulation method, and were found to have spherical shape (transmission electron microscopy studies), desirable size (90% drug was released at 39°C after 5 hours, suggesting that the SLNs show thermoresponsive drug release, thus confirming our hypothesis. Drug release from SLNs at 39°C was similar to oleic acid and linoleic acid nanoemulsions used in this study, which further confirmed that thermoresponsive drug release is due to solid–liquid phase transition. Next, a differential pulse voltammetry-based electrochemical chemical detection method was developed for quick and real-time analysis of 5-FU release, which also confirmed thermoresponsive drug release behavior of SLNs. Blank SLNs were found to be biocompatible with human gingival fibroblast cells, although 5-FU-loaded SLNs showed some cytotoxicity after 24 hours. 5-FU-loaded SLNs showed thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity was higher at 39°C (cell viability 72%–78%) compared to 37°C (cell viability >90%) within 1 hour. In conclusion, this study presents SLNs as a safe, simple, and effective platform for thermoresponsive targeting. Keywords: temperature sensitive, breast cancer, 5-fluorouracil, nanostructured lipid carriers, emulsions, fatty acids

Novel dual‐responsive hydrogels of semi‐interpenetrating polymer networks (semi‐IPNs) based on temperature‐sensitive N‐isopropylacrylamide (NIPAA) and pH‐sensitive N‐ethylmaleamic acid (NEMA) monomers and sodium alginate polymer were synthesized using free‐radical polymerization in the presence of N,N′‐methylenebisacrylamide as a crosslinker. Stimuli‐responsive properties of the semi‐IPN hydrogels showed remarkable sensitivity to both temperature and pH without limitation in NEMA content. Doxorubicin hydrochloride (DOX) as a model drug was efficiently loaded into the hydrogels and the release profiles of drug from them were investigated. The results of in vitro studies showed a quick DOX release in the conditions simulating tumor environment (phosphate‐buffered saline [PBS], pH 6.5, 37°C) or endosomes/lysosomes (PBS, pH 5.5, 37°C) compared to simulated human physiological conditions (PBS, pH 7.4, 37°C). In conclusion, the novel poly(NIPAA‐co‐NEMA) semi‐IPN hydrogels could be a promising candidate for targeted and controlled release of anticancer drugs in drug delivery system. [ABSTRACT FROM AUTHOR]

Bathing suit ichthyosis (BSI) is a rare, autosomal recessive form of congenital ichthyosis. The phenotypic expression of this unique form of ichthyosis is limited to the involvement of bathing suit area owing to the temperature-sensitive mutation of transglutaminase 1 gene. Lack of Indian literature of this rare condition made us to report three cases of BSI in healthy female children who presented with ichthyotic scales on the trunk since birth with sparing of extremities.

Viral genomic RNA encapsidated by nucleoprotein (N) forms functional template for the transcription and replication of vesicular stomatitis virus (VSV). The crystal structure of the N-RNA complex shows that RNA is tightly sequestered between the two lobes of the N protein. The residue (R7) in N-terminal arm of N is of great importance to the formation of functional N-RNA template. In our study, we found that single amino acid substitution (R7A) resulted in the loss of CAT expression in vitro minigenome system at 37 °C. But the R7A had little effect on CAT expression at 31 °C. Further analysis showed that R7A had great effects on the RNA synthesis and the formation of cytoplasmic inclusions of VSV only at 37 °C not at 31 °C. For the further investigation of the effect of R7A on virus replication, we checked the dominant-negative effect of NR7A in minigenome system and the single step curve of recombinant virus with R7A mutation in N protein (rVSVR7A) under 37 °C and 31 °C separately. Our results showed that the mutation of R7A within the N-terminal arm of N affected both replication and transcription and induced VSV to become temperature sensitive. [ABSTRACT FROM AUTHOR]

This investigation aims to develop bacterial-resistant temperature-sensitive semi-IPN silver composite hydrogels via a three-step method. Primarily, the temperature-sensitive semi-IPN hydrogels of N -isopropylacrylamide and various concentrations of Pluronic F-127 (PF 127), have been prepared via a free radical polymerization technique. Furthermore, silver ions were encapsulated in the temperature-sensitive semi-IPN hydrogels via the swelling process. Finally, the bacterial-resistant semi-IPN silver composite hydrogels were developed by using an aqueous neem extract as a reducing agent. Semi-IPN hydrogels with higher amount of PF-127 showed a water uptake that was three times better than the pristine poly (N -isopropylacrylamide). The phase transition temperature of the semi-IPN silver composite hydrogels was found to be 34.24 °C, which was confirmed from the swelling and the DSC studies. The resulting hydrogels were characterized by: FTIR, UV–vis, X-ray diffraction, SEM and TEM analyses. The TEM results confirmed the fact that the nanoparticles formed were of spherical shape with a dimension of ˜8 ± 2 nm. The semi-IPN silver-composite hydrogels showed excellent bacteria inhibition against gram-positive bacteria. The results demonstrated that the temperature-sensitive semi-IPN silver-composite hydrogels developed can be employed for clinical applications. [ABSTRACT FROM AUTHOR]

Ocular Drug Delivery has been a major challenging and interesting field for the pharmaceutical scientist due to unique anatomy and physiology of eye. The eye suffers from various problems like glaucoma, dry eye syndrome, keratitis, endopthalmitis, trachoma and conjunctivitis. To achieve the effective ocular therapy within the eye. An adequate amount of active ingredients must be delivered and maintained at the site of action. The conventional therapy exhibits the poor bioavailability due to the rapid precorneal drug loss. There are some static and dynamic barriers which also affect the bioavailability of drug. There are considerable efforts which are directed towards newer drug system for ocular administration to overcome the drawbacks of conventional therapy. The use of in situ overcomes the problems when drop instilled into the eye it undergoes sol-gel transition and transition form in cul-de-sac. This review involves in-situ gel system which includes thermally triggered system, pH triggered system and ion cross linking system. It involves detailed method of preparation and evaluation parameters of pH triggered system. [ABSTRACT FROM AUTHOR]

The purpose of this pilot study was to analyse the current cold chain storage methods of Class 8 stores, specifically thermolabile medications and temperature-sensitive diagnostics, dressings and fluids, for the Australian Army in a training area within Australia. This research was designed to identify deficiencies in current storage methods, including the inability to maintain recommended temperatures of pharmaceuticals in accordance with the Therapeutic Goods Administration (TGA), as well as foster communication between key stakeholders, such as the Royal Australian Army Medical Corps and the Department of Defence Joint Health Command, to develop a cold-chain protocol specific for the Australian Army. This pilot study identified the common occurrence of breaches in a specific climate, resulting in thermolabile medications, and temperature-sensitive diagnostics, dressings and fluids being commonly exposed to temperatures outside the range recommended by manufacturers. The study's findings relate mainly to the current storage equipment for Class 8 stores used by the Australian Army and, as a result, recommends the replacement of this mission essential equipment to ensure that cold chain storage meets the TGA guidelines. The study discusses the need for clearly defined guidelines with accountability on the stakeholders to ensure the provision of health support to all Australian Defence Force (ADF) personnel in the field is in accordance with the standard of care expected at a civilian health facility. [ABSTRACT FROM AUTHOR]