Large language model for horizontal transfer of resistance gene: From resistance gene prevalence detection to plasmid conjugation rate evaluation.

The burgeoning issue of plasmid-mediated resistance genes (ARGs) dissemination poses a significant threat to environmental integrity. However, the prediction of ARGs prevalence is overlooked, especially for emerging ARGs that are potentially evolving gene exchange hotspot. Here, we explored to classify plasmid or chromosome sequences and detect resistance gene prevalence by using DNABERT. Initially, the DNABERT fine-tuned in plasmid and chromosome sequences followed by multilayer perceptron (MLP) classifier could achieve 0.764 AUC (Area under curve) on external datasets across 23 genera, outperforming 0.02 AUC than traditional statistic-based model. Furthermore, Escherichia, Pseudomonas single genera based model were also be trained to explore its predict performance to ARGs prevalence detection. By integrating K-mer frequency attributes, our model could boost the performance to predict the prevalence of ARGs in an external dataset in Escherichia with 0.0281-0.0615 AUC and Pseudomonas with 0.0196-0.0928 AUC. Finally, we established a random forest model aimed at forecasting the relative conjugation transfer rate of plasmids with 0.7956 AUC, drawing on data from existing literature. It identifies the plasmid's repression status, cellular density, and temperature as the most important factors influencing transfer frequency. With these two models combined, they provide useful reference for quick and low-cost integrated evaluation of resistance gene transfer, accelerating the process of computer-assisted quantitative risk assessment of ARGs transfer in environmental field.

Programmable ultrasound imaging guided theranostic nanodroplet destruction for precision therapy of breast cancer.

Ultrasound-stimulated contrast agents have gained significant attention in the field of tumor treatment as drug delivery systems. However, their limited drug-loading efficiency and the issue of bulky, imprecise release have resulted in inadequate drug concentrations at targeted tissues. Herein, we developed a highly efficient approach for doxorubicin (DOX) precise release at tumor site and real-time feedback via an integrated strategy of "programmable ultrasonic imaging guided accurate nanodroplet destruction for drug release" (PND). We synthesized DOX-loaded nanodroplets (DOX-NDs) with improved loading efficiency (15 %) and smaller size (mean particle size: 358 nm). These DOX-NDs exhibited lower ultrasound activation thresholds (2.46 MPa). By utilizing a single diagnostic transducer for both ultrasound stimulation and imaging guidance, we successfully vaporized the DOX-NDs and released the drug at the tumor site in 4 T1 tumor-bearing mice. Remarkably, the PND group achieved similar tumor remission effects with less than half the dose of DOX required in conventional treatment. Furthermore, the ultrasound-mediated vaporization of DOX-NDs induced tumor cell apoptosis with minimal damage to surrounding normal tissues. In summary, our PND strategy offers a precise and programmable approach for drug delivery and therapy, combining ultrasound imaging guidance. This approach shows great potential in enhancing tumor treatment efficacy while minimizing harm to healthy tissues.

Ionizable copolymer functionalized magnetic nanocomposite as an adsorbent for boosting the extraction selectivity of aristolochic acids.

Aristolochic acid nephropathy (AAN) has drawn increasing public attention. Organic anion transporters (OATs) are considered to be responsible for mediating nephrotoxicity of aristolochic acids (AAs), as AAs are typical OAT1 substrates that exhibit anionic properties and contain one hydrophobic domain. Inspired by the OAT1 three-dimensional structure or substrate/protein interactions involved in transport, we designed a magnetic polymeric hybrid, mimicking the effect of basic and aromatic residues of OAT1, for efficient enriching aristolochic acid I (AA I) and aristolochic acid II (AA II) in Traditional Chinese patent medicines (TCPM). N, N-dimethylaminopropyl acrylamide (DMAPAm) was used as a cationic monomer and copolymerized with divinylbenzene (DVB) onto the surface of monodisperse magnetic nanoparticles (denoted as MNs@SiO2T-DvbDam). The magnetic polymer hybrid demonstrated high selectivity and capacity for AAs, which was mainly attributed to (1) electrostatic interactions from the cationic or basic moiety of DMAPAm and (2) the hydrophobic and π-π stacking interactions from the aromatic ring of DVB. Additionally, the surface of the hybrid exhibited amphiphilic property according to the ionization of DMAPAm, thus improving the compatibility of the adsorbent with the aqueous sample matrix. This strategy was proven to be robust in the analysis of real drug samples, which was characterized by a good linearity, high recovery and satisfactory reusability. This work confirmed that the proposed tool could be a promising candidate for enhancing the extraction selectivity of AAs in Traditional Chinese medicines (TCM).

3D Printing of a Vascularized Mini-Liver Based on the Size-Dependent Functional Enhancements of Cell Spheroids for Rescue of Liver Failure.

The emerging stem cell-derived hepatocyte-like cells (HLCs) are the alternative cell sources of hepatocytes for treatment of highly lethal acute liver failure (ALF). However, the hostile local environment and the immature cell differentiation may compromise their therapeutic efficacy. To this end, human adipose-derived mesenchymal stromal/stem cells (hASCs) are engineered into different-sized multicellular spheroids and co-cultured with 3D coaxially and hexagonally patterned human umbilical vein endothelial cells (HUVECs) in a liver lobule-like manner to enhance their hepatic differentiation efficiency. It is found that small-sized hASC spheroids, with a diameter of ≈50 µm, show superior pro-angiogenic effects and hepatic differentiation compared to the other counterparts. The size-dependent functional enhancements are mediated by the Wnt signaling pathway. Meanwhile, co-culture of hASCs with HUVECs, at a HUVECs/hASCs seeding density ratio of 2:1, distinctly promotes hepatic differentiation and vascularization both in vitro and in vivo, especially when endothelial cells are patterned into hollow hexagons. After subcutaneous implantation, the mini-liver, consisting of HLC spheroids and 3D-printed interconnected vasculatures, can effectively improve liver regeneration in two ALF animal models through amelioration of local oxidative stress and inflammation, reduction of liver necrosis, as well as increase of cell proliferation, thereby showing great promise for clinical translation.

Pattern recognition of microcirculation with super-resolution ultrasound imaging provides markers for early tumor response to anti-angiogenic therapy.

Rationale: Cancer treatment outcome is traditionally evaluated by tumor volume change in clinics, while tumor microvascular heterogeneity reflecting tumor response has not been fully explored due to technical limitations. Methods: We introduce a new paradigm in super-resolution ultrasound imaging, termed pattern recognition of microcirculation (PARM), which identifies both hemodynamic and morphological patterns of tumor microcirculation hidden in spatio-temporal space trajectories of microbubbles. Results: PARM demonstrates the ability to distinguish different local blood flow velocities separated by a distance of 24 µm. Compared with traditional vascular parameters, PARM-derived heterogeneity parameters prove to be more sensitive to microvascular changes following anti-angiogenic therapy. Particularly, PARM-identified "sentinel" microvasculature, exhibiting evident structural changes as early as 24 hours after treatment initiation, correlates significantly with subsequent tumor volume changes (|r| > 0.9, P < 0.05). This provides prognostic insight into tumor response much earlier than clinical criteria. Conclusions: The ability of PARM to noninvasively quantify tumor vascular heterogeneity at the microvascular level may shed new light on early-stage assessment of cancer therapy.

Silk Fibroin-Coated Nano-MOFs Enhance the Thermal Stability and Immunogenicity of HBsAg.

Vaccines are widely regarded as one of the most effective weapons in the fight against infectious diseases. Currently, vaccines must be stored and transported at low temperatures as high temperatures can lead to a loss of vaccine conformation and reduced therapeutic efficacy. Metal-organic frameworks (MOFs), such as zeolitic imidazole framework-8 (ZIF-8), are a new class of hybrid materials with large specific surface areas, high loading rates, and good biocompatibility and are successful systems for vaccine delivery and protection. Silk fibroin (SF) has a good biocompatibility and thermal stability. In this study, the hepatitis B surface antigen (HBsAg) was successfully encapsulated in ZIF-8 to form HBsAg@ZIF-8 (HZ) using a one-step shake and one-pot shake method. Subsequently, the SF coating modifies HZ through hydrophobic interactions to form HBsAg/SF@ZIF-8 (HSZ), which enhanced the thermal stability and immunogenicity of HBsAg. Compared to free HBsAg, HZ and HSZ improved the thermostability of HBsAg, promoted the antigen uptake and lysosomal escape, stimulated dendritic cell maturation and cytokine secretion, formed an antigen reservoir to promote antibody production, and activated CD4+ T and CD8+ T cells to enhance memory T-cell production. Importantly, HSZ induced a strong immune response even after 14 days of storage at 25 °C. Furthermore, the nanoparticles prepared by the one-step shake method exhibited superior properties compared to those prepared by the one-pot shake method. This study highlights the importance of SF-coated ZIF-8, which holds promise for investigating thermostable vaccines and breaking the vaccine cold chain.

A new application of nano-selenium: rescue of CK2 and mitochondria from oxidative stress to prevent cardiac hypertrophy.

Background: Excessive reactive oxygen species (ROS) and subsequent mitochondrial dysfunction are pivotal in initiating cardiac hypertrophy. To explore nano-selenium's (SeNP's) preventive potential against this condition, the authors evaluated chemically synthesized chitosan-SeNPs and biosynthesized Bacillus cereus YC-3-SeNPs in an angiotensin II (Ang II)-induced cardiac hypertrophy model. Methods: This investigation encompassed ROS measurement, mitochondrial membrane potential analysis, transmission electron microscopy, gene and protein expression analyses, protein carbonylation assays, serum antioxidant quantification and histological staining. Results: SeNPs effectively countered Ang II-induced cardiac hypertrophy by reducing ROS, restoring mitochondrial and protein kinase 2α (CK2-α) function, activating antioxidant pathways and enhancing serum antioxidant levels. Conclusion: This finding underscores SeNPs' role in attenuating Ang II-induced myocardial hypertrophy both in vitro and in vivo.

Enlargement of the heart is called cardiac hypertrophy; this is caused by too many reactive oxygen species, which are compounds that damage the mitochondria of cells. The mitochondria provide energy to cells and their disruption can cause a significantly negative effect on cells and the tissues and organs cells make up. Selenium is a type of metal that must be consumed in small amounts to stay healthy; it has antioxidant effects, meaning it can stop reactive oxygen species and potentially prevent cardiac hypertrophy. Nano-selenium (SeNP), consisting of tiny, spherical particles containing selenium, may be a more effective way of delivering selenium as an antioxidant to prevent cardiac hypertrophy. SeNPs were made synthetically and from a type of bacterium called Bacillus cereus; both SeNPs demonstrated antioxidant effects in heart cells taken from chicken embryos and live chickens. These results suggest that SeNPs could be developed into medication to combat cardiac hypertrophy.

The genetic structure and demographic history revealed by whole-genome resequencing provide insights into conservation of critically endangered Artocarpus nanchuanensis.

Introduction: Whole-genome resequencing technology covers almost all nucleotide variations in the genome, which makes it possible to carry out conservation genomics research on endangered species at the whole-genome level. Methods: In this study, based on the whole-genome resequencing data of 101 critically endangered Artocarpus nanchuanensis individuals, we evaluated the genetic diversity and population structure, inferred the demographic history and genetic load, predicted the potential distributions in the past, present and future, and classified conservation units to propose targeted suggestions for the conservation of this critically endangered species. Results: Whole-genome resequencing for A. nanchuanensis generated approximately 2 Tb of data. Based on abundant mutation sites (25,312,571 single nucleotide polymorphisms sites), we revealed that the average genetic diversity (nucleotide diversity, π) of different populations of A. nanchuanensis was relatively low compared with other trees that have been studied. And we also revealed that the NHZ and QJT populations harboured unique genetic backgrounds and were significantly separated from the other five populations. In addition, positive genetic selective signals, significantly enriched in biological processes related to terpene synthesis, were identified in the NHZ population. The analysis of demographic history of A. nanchuanensis revealed the existence of three genetic bottleneck events. Moreover, abundant genetic loads (48.56% protein-coding genes) were identified in Artocarpus nanchuanensis, especially in genes related to early development and immune function of plants. The predication analysis of suitable habitat areas indicated that the past suitable habitat areas shifted from the north to the south due to global temperature decline. However, in the future, the actual distribution area of A. nanchuanensis will still maintain high suitability. Discussion: Based on total analyses, we divided the populations of A. nanchuanensis into four conservation units and proposed a number of practical management suggestions for each conservation unit. Overall, our study provides meaningful guidance for the protection of A. nanchuanensis and important insight into conservation genomics research.

Microneedle system for tissue engineering and regenerative medicine.

Global increasing demand for high life quality and length facilitates the development of tissue engineering and regenerative medicine, which apply multidisciplinary theories and techniques to achieve the structural reconstruction and functional recovery of disordered or damaged tissues and organs. However, the clinical performances of adopted drugs, materials, and powerful cells in the laboratory are inescapably limited by the currently available technologies. To tackle the problems, versatile microneedles are developed as the new platform for local delivery of diverse cargos with minimal invasion. The efficient delivery, as well as painless and convenient procedure endow microneedles with good patient compliance in clinic. In this review, we first categorize different microneedle systems and delivery models, and then summarize their applications in tissue engineering and regenerative medicine mainly involving maintenance and rehabilitation of damaged tissues and organs. In the end, we discuss the advantages, challenges, and prospects of microneedles in depth for future clinical translations.

Stem cell-derived hepatocyte therapy using versatile biomimetic nanozyme incorporated nanofiber-reinforced decellularized extracellular matrix hydrogels for the treatment of acute liver failure.

Reactive oxygen species (ROS)-associated oxidative stress, inflammation storm, and massive hepatocyte necrosis are the typical manifestations of acute liver failure (ALF), therefore specific therapeutic interventions are essential for the devastating disease. Here, we developed a platform consisting of versatile biomimetic copper oxide nanozymes (Cu NZs)-loaded PLGA nanofibers (Cu NZs@PLGA nanofibers) and decellularized extracellular matrix (dECM) hydrogels for delivery of human adipose-derived mesenchymal stem/stromal cells-derived hepatocyte-like cells (hADMSCs-derived HLCs) (HLCs/Cu NZs@fiber/dECM). Cu NZs@PLGA nanofibers could conspicuously scavenge excessive ROS at the early stage of ALF, and reduce the massive accumulation of pro-inflammatory cytokines, herein efficiently preventing the deterioration of hepatocytes necrosis. Moreover, Cu NZs@PLGA nanofibers also exhibited a cytoprotection effect on the transplanted HLCs. Meanwhile, HLCs with hepatic-specific biofunctions and anti-inflammatory activity acted as a promising alternative cell source for ALF therapy. The dECM hydrogels further provided the desirable 3D environment and favorably improved the hepatic functions of HLCs. In addition, the pro-angiogenesis activity of Cu NZs@PLGA nanofibers also facilitated the integration of the whole implant with the host liver. Hence, HLCs/Cu NZs@fiber/dECM performed excellent synergistic therapeutic efficacy on ALF mice. This strategy using Cu NZs@PLGA nanofiber-reinforced dECM hydrogels for HLCs in situ delivery is a promising approach for ALF therapy and shows great potential for clinical translation.

Preparation, characterization, and antioxidant and antiapoptotic activities of biosynthesized nano­selenium by yak-derived Bacillus cereus and chitosan-encapsulated chemically synthesized nano­selenium.

Nano­selenium (SeNPs) is a red elemental selenium with extremely small particles, which can be absorbed by the body and has biological activity. Currently, the most commonly used synthetic methods for SeNPs are biosynthesis and chemical synthesis. In this study, YC-3-SeNPs were biosynthesized by a strain of yak-gut Bacillus cereus YC-3, and meanwhile, CST-SeNPs were chemically synthesized and encapsulated with chitosan. A series of characterizations proved that YC-3-SeNPs and CST-SeNPs are spherical particles with excellent stability, and both have an excellent ability to scavenge free radicals in vitro. The particles of YC-3-SeNPs were encapsulated with polysaccharides, fiber, and protein, and it was less toxic than that of CST-SeNPs. Additionally, YC-3-SeNPs and CST-SeNPs may inhibit H2O2-induced oxidative stress in cardiomyocytes by activating the Keap1/Nrf2/HO-1 signaling pathway thereby scavenging ROS. Meanwhile, they may exert anti-apoptotic activity in cardiomyocytes by stabilizing mitochondrial membrane potential (∆Ψm) and balancing Bax/Bcl-2 protein, thereby reducing the protein expression of Cyt-c and Cleaved-caspase 3. Given the above, YC-3-SeNPs and CST-SeNPs with excellent antioxidant and anti-apoptotic activities may have broad application potential in the field of cardiovascular diseases.

Thiazolylazopyrazoles as Nonsymmetric Bis-Heteroaryl Azo Switches: High-Yield Visible-Light Photoisomerization and Increased Z-Isomer Stability by o-Carbonylation.

Following the progress on mono-heteroaryl azo switches (Het-N=N-Ph), a few bis-heteroaryl azo switches (Het-N=N-Het) have been studied recently, whereas the nonsymmetric bis-heteroaryl ones (Het1 -N=N-Het2 ) that can combine the respective merits of each heterocycle, have received little attention. Here we report thiazolylazopyrazoles as nonsymmetric bis-heteroaryl azo switches that combine the visible-light switching character of the thiazole ring and the ease of o-substitution of the pyrazole ring. Thiazolylazopyrazoles can achieve (near-)quantitative visible-light isomerization in both directions and long Z-isomer thermal half-lives of several days. In contrast to the drastically destabilizing effect of o-methylation, o-carbonylation of the pyrazole ring can remarkably stabilize Z isomers by inducing attractive intramolecular interactions (dispersion, C-H⋅⋅⋅N bond, and lone-pair⋅⋅⋅π interaction). Our work highlights the importance of the rational combination of two heterocycles and suitable structural substitution in developing bis-heteroaryl azo switches.

Complete mitochondrial genome of Thuja sutchuenensis and its implications on evolutionary analysis of complex mitogenome architecture in Cupressaceae.

BACKGROUND: The complex physical structure and abundant repeat sequences make it difficult to assemble the mitogenomes of seed plants, especially gymnosperms. Only approximately 33 mitogenomes of gymnosperms have been reported. However, as the most widely distributed and the second largest family among gymnosperms, Cupressaceae has only six assembled mitogenomes, including five draft mitogenomes and one complete mitogenome, which has greatly hindered the understanding of mitogenome evolution within this large family, even gymnosperms. RESULTS: In this study, we assembled and validated the complete mitogenome of Thuja sutchuenensis, with a size of 2.4 Mb. Multiple sequence units constituted its complex structure, which can be reduced to three linear contigs and one small circular contig. The analysis of repeat sequences indicated that the numbers of simple sequence repeats increased during the evolutionary history of gymnosperms, and the mitogenome of Thuja sutchuenensis harboured abundant extra-long repeats (more than 5 kb). Additionally, the longest repeat sequence identified in these seven gymnosperms also came from the mitogenome of Thuja sutchuenensis, with a length of up to 47 kb. The analysis of colinear blocks and gene clusters both revealed that the orders of mitochondrial genes within gymnosperms was not conserved. The comparative analysis showed that only four tRNAs were shared by seven gymnosperms, namely, trnD-GUC, trnE-UUC, trnI-CAU and trnY-GUA. Furthermore, four genes have undergone potential positive selection in most gymnosperm species, namely, atp8, ccmB, mttB and sdh4. CONCLUSION: We successfully assembled the second complete mitogenome within Cupressaceae and verified that it consisted of multiple sequence units. Our study also indicated that abundant long repeats may contribute to the generation of the complex conformation of the mitogenome of Thuja sutchuenensis. The investigation of Thuja sutchuenensis's mitogenome in our study provides new insight into further understanding the complex mitogenome architecture within gymnosperms.

Highly efficient fabrication of functional hepatocyte spheroids by a magnetic system for the rescue of acute liver failure.

Engineering hepatocytes as multicellular cell spheroids can improve their viability after implantation in vivo for effective rescue of the devastating acute liver failure (ALF). However, there is still a lack of straightforward methods for efficient generation of functional hepatocyte spheroids. In this study, a magnetic system, consisting of magnetic microwell arrays and magnet blocks, is developed to realize magnetically controlled 3D cell capture and spatial confinement-mediated cell aggregation. The cell spheroids with smaller size show superior hepatic functions than the larger-sized counterparts. Notably, the intrinsic magnetism of magnetic microwell arrays can regulate superoxide anions in hepatocyte spheroids and herein promote various biological processes, including antioxidation, hepatocyte-related functions, and pro-angiogenic potential. Ectopic implantation of the functional cell spheroids in ALF-challenged mice significantly prolongs the animal survival, ameliorates inflammation, and promotes liver regeneration. Hence, application of the magnetic system for generation of functionally enhanced hepatocyte spheroids holds great potential for clinical translation in the future.

Ultrasound-Mediated Antitumor Therapy via Targeted Acoustic Release Carrier of Carbon Monoxide (TARC-CO).

As one of the most valuable endogenous gas signaling molecules, carbon monoxide (CO) has been demonstrated in numerous studies to show excellent promise in the treatment of diseases, such as cancer. However, for many years, the inherent high affinity of CO for hemoglobin severely impeded the clinical transformation of CO-based treatments. Therefore, the controlled delivery of CO to target tissues has become a common challenge. Herein, an efficient ultrasonic-triggered and targeted CO release strategy was constructed based on a novel targeted acoustic release carrier of carbon monoxide (TARC-CO) that we synthesized in this study. The designed TARC-COs could afford a safe, stable, and ultrasound-guided delivery of CO in vivo by loading a specified dose of CO inside microbubbles, resulting in breast tumor suppression. Taking advantage of the high loading capacity of microbubbles, the unit volume of TARC-CO suspension could encapsulate up to 337.1 ± 8.0 (×103 ppm) of CO. In addition, the satisfactory ultrasound contrast-enhanced ability of TARC-COs achieved real-time interactive guidance and visual policing of CO delivery. For the in vitro antitumor study, TARC-COs with ultrasonic irradiation were demonstrated to effectively induce mitochondrial dysfunction by reducing mitochondrial membrane potential, leading to the apoptosis of 4T1 cells. In addition, we realized that TARC-CO-based treatment could significantly slow the growth rate of tumors by inducing apoptosis, inhibiting the proliferation of cancer cells, and limiting tumor angiogenesis. In summary, this proof-of-concept study demonstrates the feasibility and tremendous potential of TARC-COs for controlled release of CO, which can be expected to provide new inspirations and a promising perspective for therapy based on active gases.

Dopant-Free Bithiophene-Imide-Based Polymeric Hole-Transporting Materials for Efficient and Stable Perovskite Solar Cells.

The development of hole-transport materials (HTMs) with high mobility, long-term stability, and comprehensive passivation is significant for simultaneously improving the efficiency and stability of perovskite solar cells (PVSCs). Herein, two donor-acceptor (D-A) conjugated polymers PBTI and PFBTI with alternating benzodithiophene (BDT) and bithiophene imide (BTI) units are successfully developed with desirable hole mobilities due to the good planarity and extended conjugation of molecular backbone. Both copolymers can be employed as HTMs with suitable energy levels and efficient defect passivation. Shortening the alkyl chain of the BTI unit and introducing fluorine atoms on the BDT moiety effectively enhances hole mobility and hydrophobicity of the HTMs, leading to improved efficiency and stability of PVSCs. As a result, the organic-inorganic hybrid PVSCs with PFBTI as the HTM deliver a power conversion efficiency (PCE) of 23.1% with enhanced long-term operational and ambient stability, which is one of the best efficiencies reported for PVSCs with dopant-free polymeric HTMs to date. Moreover, PFBTI can be applied in inorganic PVSCs and perovskite/organic tandem solar cells, achieving a high PCE of 17.4% and 22.2%, respectively. These results illustrate the great potential of PFBTI as an efficient and widely applicable HTM for cost-effective and stable PVSCs.

Enhanced Acoustic Droplet Vaporization through the Active Magnetic Accumulation of Drug-Loaded Magnetic Particle-Encapsulated Nanodroplets (MPE-NDs) in Cancer Therapy.

The application of drug-loaded nanodroplets is still limited by their insufficient accumulation owing to the enhanced permeability and retention (EPR) effect failure in cancer therapy. To overcome these limitations, we propose an alternative magnetic particle-encapsulated nanodroplet (MPE-ND) with outstanding biosafety and magnetic targeting by encapsulating fluorinated Fe3O4-SiO2 nanoparticles inside the liquid core of the nanodroplets. Meanwhile, doxorubicin (DOX) can be stably loaded into the shell through both electrostatic and hydrophobic interactions to obtain drug-loaded MPE-NDs. Both in vitro and in vivo experiments have consistently demonstrated that drug-loaded MPE-NDs can significantly increase the local drug concentration and enhance the damage of tumor tissues through acoustic droplet vaporization under a static magnetic field (eADV therapy). Histological examination reveals that eADV therapy efficiently suppresses tumor proliferation by inducing apoptosis, destroying supply vessels, and inhibiting neovascularization. Drug-loaded MPE-NDs can be expected to open a new gateway for ultrasound-triggered drug delivery and cancer treatment.

Facile Synthesis of Sugar Nucleotides from Common Sugars by the Cascade Conversion Strategy.

Sugar nucleotides are essential glycosylation donors in the carbohydrate metabolism. Naturally, most sugar nucleotides are derived from a limited number of common sugar nucleotides by de novo biosynthetic pathways, undergoing single or multiple reactions such as dehydration, epimerization, isomerization, oxidation, reduction, amination, and acetylation reactions. However, it is widely believed that such complex bioconversions are not practical for synthetic use due to the high preparation cost and great difficulties in product isolation. Therefore, most of the discovered sugar nucleotides are not readily available. Here, based on de novo biosynthesis mainly, 13 difficult-to-access sugar nucleotides were successfully prepared from two common sugars D-Man and sucrose in high yields, at a multigram scale, and without the need for tedious purification manipulations. This work demonstrated that de novo biosynthesis, although undergoing complex reactions, is also practical and cost-effective for synthetic use by employing a cascade conversion strategy.

Probiotic Potential of Bacillus licheniformis and Bacillus pumilus Isolated from Tibetan Yaks, China.

Yak (Bos grunniens) inhabit an oxygen-deficient environment at the altitude of 3000 m on the Tibetan Plateau, with a distinctive gut micro-ecosystem. This study evaluated the probiotic potential and physiological property of Bacillus licheniformis and Bacillus pumilus isolated from the gut of yaks. Four strains, two Bacillus licheniformis (named D1 and D2) and two Bacillus pumilus (named X1 and X2), were isolated and identified by 16S rRNA sequencing. All strains had potential antibacterial ability against three indicator pathogens: Escherichia coli C83902, Staphylococcus aureus BNCC186335, and Salmonella enteritidis NTNC13349. The antioxidant activity test showed that D2 sample showed the highest antioxidant activity. Furthermore, all four strains had a higher hydrophobicity, auto-aggregation, acid tolerance, bile tolerance, and antibiotic sensitivity, which all contribute to their survival in the gastrointestinal tract and clinical utility. The animal experimentation (40 KM mice, equally divided into five groups of eight mice each) showed that the strain supplementation not only increased daily weight gain and reduced feed conversion ratio, but also increased the length of the jejunum villi and the value of the V/C (Villi/Crypt). In conclusion, this is the first study demonstrated the probiotic potential of Bacillus licheniformis and Bacillus pumilus isolated from yaks, providing a theoretical basis for the clinical application and development of new feed additives.

Real-Time Monitoring of Intraocular Pressure in Glaucoma Patients Using Wearable Mobile Medicine Devices.

Glaucoma is caused by excessive aqueous humor in the eye, resulting in a continuous or intermittent increase of intraocular pressure, which exceeds the tolerance of the eyeball and damages the optic nerve. Existing treatments for glaucoma do not work well or have significant side effects. Intraocular pressure signal is a very important physiological signal that needs real-time and accurate monitoring in glaucoma patients, especially in severe glaucoma patients. Therefore, long-term, real-time, and accurate monitoring of intraocular pressure is of great significance for the diagnosis and treatment of glaucoma patients. The use of wearable devices for real-time ocular diagnosis and treatment of glaucoma patients is an effective approach. However, the current commonly used intraocular pressure measurement and monitoring technology is difficult to meet the diagnosis and monitoring needs of glaucoma patients in terms of size, measurement accuracy, power consumption, and intelligence. Therefore, facing the needs of glaucoma disease treatment, this topic studies an implantable flexible intraocular pressure sensor for long-term continuous monitoring of intraocular pressure in glaucoma patients and mainly focuses on the working principle, structural design, process fabrication, measurement and control system, characterization, and performance test of the intraocular pressure sensor. It is of great significance for personalized and accurate treatment of glaucoma patients.