The ß-Ketoacyl-ACP Synthase FabF Catalyzes Carbon-Carbon Bond Formation in a Bimodal Pattern for Fatty Acid Biosynthesis.

Fatty acids produced by the type-II fatty acid biosynthesis pathway (FAS-II) are essential biomaterials for bacterial membrane construction and numerous metabolic routes. The ß-ketoacyl-ACP synthase FabF catalyzes the key C-C bond formation step for fatty acid extension in FAS-II. Here, we revealed the substrate recognition and catalytic mechanisms of FabF by determining FabF-ACP complexes. FabF displays a distinctive bimodal catalytic pattern specifically on C6 and C10 acyl-ACP substrates. It utilizes positively charged residues located on the η3-helix and loop1 regions near the catalytic tunnel entrance to bind ACP, and two hydrophobic cavities as well as "front", "middle", and "back" door residues to specifically stabilize C6 and C10 acyl substrates for preferential catalysis. Further quantum chemistry calculations suggest that the FabF catalytic residues Lys336 and His304 facilitate proton transfer during condensation catalysis and C-C bond formation. Our results provide key mechanistic insights into the biosynthesis of molecular carbon skeletons based on ketosynthases that are highly conserved through the FAS and polyketide synthase (PKS) analogous biosynthetic routes, broaden the understanding of the tricarboxylic acid cycle that utilizes lipoic acid derived from C8-ACP accumulated due to the FabF distinctive catalytic pattern for oxidative decarboxylations, and may facilitate the development of narrow-spectrum antibacterial drugs.

Microcrack behavior in bone: Stress field analysis at osteon cement line tips.

Bone microstructure governs microcrack propagation complexity. Current research, relying on linear elastic fracture mechanics, inadequately considers authentic multi-level structures, like cement lines and osteons, impacting stress intensity at cracks. This study, by constructing models encompassing single or multiple osteons, delves into the influence of factors like crack length, osteon radius, and modulus ratio on the stress intensity factor at the crack tip. Employing a fracture mechanics phase-field approach to simulate crack propagation paths, it particularly explores the role of cement lines as weak interfaces in crack extension. The aim is to comprehensively and systematically elucidate the critical factors of bone microstructure in the context of crack propagation.

[Multidimensional supportive psychological intervention in clinical practice teaching of andrological nursing].

OBJECTIVE: To examine the application of a novel pedagogical approach multidimensional supportive psychological intervention (MSPI) in the clinical practice teaching of andrological nursing care. METHODS: Using the Hamilton Depression Scale (HAMD), we assessed the psychology of 100 nursing interns about to enter clinical practice in the Department of Andrology from December 2021 to December 2022. We equally randomized the subjects into an experimental and a control group, the former receiving MSPI and the latter trained on the conventional teaching model without any psychological support intervention. RESULTS: Compared with the baseline, the HAMD scores were significantly decreased in the experimental group after intervention (12.4±2.1 vs 8.9±2.4, P<0.01), but increased in the controls (13.1±1.8 vs 14.7±1.9, P<0.01); the skill scores dramatically increased in the experimental group (82.6±4.7 vs 91.2±2.4, P<0.01), but decreased in the control group after intervention (81.0±3.5 vs 80.4±2.7, P = 0.28). CONCLUSION: MSPI can significantly enhance the learning enthusiasm of nursing students in a short period, reduce their psychological stress and improve teaching outcomes. This approach, combining psychology with teaching, can also strengthen the mental resilience of nursing students and better confront them with future professional challenges.

Cinquefoil Knot Possessing Dynamic and Tunable Metal Coordination.

While the majority of knots are made from the metal-template approach, the use of entangled, constrained knotted loops to modulate the coordination of the metal ions remains inadequately elucidated. Here, we report on the coordination chemistry of a 140-atom-long cinquefoil knotted strand comprising five tridentate and five bidentate chelating vacancies. The knotted loop is prepared through the self-assembly of asymmetric "3 + 2" dentate ligands with copper(II) ions that favor five-coordination geometry. The formation of the copper(II) pentameric helicate is confirmed by X-ray crystallography, while the corresponding copper(II) knot is characterized by XPS and LR-/HR ESI-MS. Upon removal of the original template, the knotted ligand facilitates zinc(II) ions, which typically form four- or six-coordination geometries, resulting in the formation of an otherwise inaccessible zinc(II) metallic knot with coordinatively unsaturated metal centers. The coordination numbers and geometries of the zinc(II) cations are undoubtedly determined by X-ray crystallography. Despite the kinetically labile nature and high reversibility of the zinc(II) complex preventing the detection of 5-to-6 coordination equilibrium in solution, the effects on metal-ion coordination induced by knotting hold promise for fine-tuning the coordination of metal complexes.

Construction of a panoramic mRNA map of adult noncystic fibrosis bronchiectasis and a preliminary study of the underlying molecular mechanisms.

BACKGROUND: The pathogenesis of noncystic fibrosis bronchiectasis in adults is complex, and the relevant molecular mechanisms remain unclear. In this study, we constructed a panoramic map of bronchiectasis mRNA, explored the potential molecular mechanisms, and identified potential therapeutic targets, thus providing a new clinical perspective for the preventive management of bronchiectasis and its acute exacerbation. METHODS: The mRNA profiles of peripheral blood and bronchiectasis tissues were obtained through transcriptome sequencing and public databases, and bioinformatics methods were used to screen for differentially expressed genes (DEGs). The DEGs were then subjected to biological function and pathway analyses. Some DEGs were validated using a real-time quantitative polymerase chain reaction (RT-qPCR) in peripheral blood. Spearman's correlation analysis was used to analyse the correlation between DEGs and clinical indicators. RESULTS: Based on transcriptome sequencing and public databases, the mRNA profile of bronchiectasis was determined. DEGs were obtained from the peripheral blood sequencing dataset (985 DEGs), tissue sequencing dataset (2919 DEGs), and GSE97258 dataset (1083 DEGs). Bioinformatics analysis showed that upregulated DEGs had enriched neutrophil-related pathways, and downregulated DEGs had enriched ribosome-related pathways. RT-qPCR testing confirmed the upregulated expression of VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 in bronchiectasis. These genes were related to many clinical parameters, such as neutrophils, C-reactive protein, and procalcitonin (P < 0.05). CONCLUSIONS: Transcriptomic methods were used to construct a panoramic map of bronchiectasis mRNA expression. The findings showed that neutrophil activation, chronic inflammation, immune regulation, impaired ribosomal function, oxidative phosphorylation, and energy metabolism disorders are important factors in the development of bronchiectasis. VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 may play important roles in the pathogenesis of bronchiectasis and are potential therapeutic targets.

Molecular Responses of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration: Integrative Insights From Multi-Omics and Clinical Imaging.

Purpose: The purpose of this study was to investigate the molecular mechanisms underlying anti-vascular endothelial growth factor (anti-VEGF) efficacy and response variability in neovascular age-related macular degeneration (nAMD) using longitudinal proteomic and metabolomic analysis alongside three-dimensional lesion measurements. Methods: In this prospective study, 54 treatment-naive patients with nAMD underwent "3+ pro re nata" (3+PRN) anti-VEGF regimens followed for at least 12 weeks. Aqueous humors were collected pre- and post-treatment for proteomic and metabolomic analysis. Three-dimensional optical coherence tomography (OCT) and OCT angiography assessed different types of nAMD lesion volumes and areas. Results: There were 1350 proteins and 1268 metabolites that were identified in aqueous humors, with 301 proteins and 353 metabolites significantly altered during anti-VEGF treatment, enriched in pathways of angiogenesis, energy metabolism, signal transduction, and neurofunctional regulation. Sixty-seven changes of (Δ) molecules significantly correlated with at least one type of ΔnAMD lesion. Notably, proteins FGA, TALDO1, and ASPH significantly decreased during treatment, with their reductions correlating with greater lesion regression in at least two lesion types. Conversely, despite that YIPF3 also showed significant downregulation, its decrease was associated with poorer regression in total nAMD lesion and subretinal hyper-reflective material. Conclusions: This study identifies FGA, TALDO1, and ASPH as potential key molecules in the efficacy of anti-VEGF therapy, whereas YIPF3 may be a key factor in poor response. The integration of longitudinal three-dimensional lesion analysis with multi-omics provides valuable insights into the mechanisms and response variability of anti-VEGF treatment in nAMD.

Oil-droplet anchors accelerate the gelation of regenerated silk fibroin-based emulsion gels.

The oil fraction will affect the aggregation behavior and structural strength of emulsion gels. In this study, the effect of the camellia oil (CO) fraction on the properties of emulsion gels stabilized by regenerated silk fibroin (RSF) was studied. The results showed that CO was essential for gel formation, with oil droplets incorporated into the RSF matrix as anchors to achieve rapid gelation of RSF. The gel hardness significantly increased from 20.03 to 53.35 g as the fraction of CO increased from 5 % to 25 %. The oxidation stability of the emulsion gels was also improved, and the peroxide value (POV) decreased from 2419.3 to 839.9 µmol/kg. As the oil fraction rose from 5 % to 25 %, the percentage of released free fatty acids decreased from 73.24 % to 59.49 % due to forming a more compact gel structure. In addition, the rheological results revealed that all emulsion gels had a shear-thinning behavior and good temperature stability in the range of 5 to 90 °C. This study provided a theoretical basis for preparing RSF-based emulsion gels, helps in the recycling of silk protein resources, and promotes the development of emulsion gel applications in the food industry.

Unveiling the role of RhoA and ferroptosis in vascular permeability: Implications for osteoarthritis.

Abnormal angiogenesis and increased vascular permeability of subchondral bone are key mechanisms related to osteoarthritis (OA). However, the precise mechanisms responsible for heightened vascular permeability in OA remain unclear. The present study used proteomics to identify protein expression in damaged subchondral bone compared with normal subchondral bone. The results suggest that Ras homolog family member A (RhoA) may be associated with the vascular permeability of subchondral bone and ferroptosis in OA. The results of analysis of clinical samples indicated a significant increase in expression of RhoA in the subchondral bone of OA. This were consistent with the proteomics findings. We found through western blotting, RT­PCR, and immunofluorescence that RhoA significantly increased the permeability of endothelial cells (ECs) by inhibiting inter­EC adhesion proteins (zona occludens­1, connexin 43 and Vascular endothelial­Cadherin) and actin filaments. Furthermore, RhoA induced ferroptosis core proteins (glutathione peroxidase 4,  solute carrier family 7 member 11 and acyl­CoA synthase long­chain family member 4, ACSL4) by influencing lipid peroxidation and mitochondrial function, leading to ferroptosis of ECs. This suggested an association between RhoA, ferroptosis and vascular permeability. Ferroptosis significantly increased permeability of ECs by inhibiting inter­EC adhesion proteins. RhoA increased vascular permeability by inducing ferroptosis of ECs. In vivo, inhibition of RhoA and ferroptosis significantly mitigated progression of OA by alleviating cartilage degeneration and subchondral bone remodeling in mice with destabilization of the medial meniscus. In conclusion, the present findings indicated that RhoA enhanced vascular permeability in OA by inducing ferroptosis. This may serve as a novel strategy for the early prevention and treatment of OA.

Enhanced degradation of phenolic pollutants by a novel cold-adapted laccase from Peribacillus simplex.

Laccase (EC 1.10.3.2), as eco-friendly biocatalysts, holds immense potential for sustainable applications across various environmental and industrial sectors. Despite the growing interest, the exploration of cold-adapted laccases, especially their unique properties and applicability, remains limited. In this study, we have isolated, cloned, expressed, and purified a novel laccase from Peribacillus simplex (GenBank: PP430751), which was derived from permafrost layer. The recombinant laccase (PsLac) exhibited optimal activity at 30 °C and a pH optimum of 3.5. Remarkably, PsLac exhibited remarkable stability in the presence of organic solvents, with its enzyme activity increasing by 20 % after being incubated in a 30 % trichloromethane solution for 12 h, compared to its initial activity. Furthermore, the enzyme preserved 100 % of its activity after undergoing eight freeze-thaw cycles. Notably, the catalytic center of PsLac contains Zn2+ instead of the typically observed Cu2+ found in other laccases, and metal-ion substitution experiments raised the catalytic efficiency to 3-fold when Zn2+ was replaced with Fe2+. Additionally, PsLac has demonstrated a proficient ability to degrade phenolic pollutants, such as hydroquinone, even at a low temperature of 16 °C, positioning it as a promising candidate for environmental bioremediation and contributing to cleaner production processes.

Total ammonia nitrogen inhibits medium-chain fatty acid biosynthesis by disrupting hydrolysis, acidification, chain elongation, substrate transmembrane transport and ATP synthesis processes.

This study used 16S rRNA gene sequencing and metatranscriptomic analysis to comprehensively illustrate how ammonia stress influenced medium-chain fatty acids (MCFA) biosynthesis. MCFA synthesis was inhibited at total ammonia nitrogen (TAN) concentrations above 1000 mg N/L. TAN stress hindered organic hydrolysis, acidification, and volatile fatty acids elongation. Chain-elongating bacteria (e.g., Clostridium_sensu_stricto_12, Clostridium_sensu_stricto_1, Caproiciproducens) abundance remained unchanged, but their activity decreased, partially due to the increased reactive oxygen species. Metatranscriptomic analysis revealed reduced activity of enzymes critical for MCFA production under TAN stress. Fatty acid biosynthesis pathway rather than reverse ß-oxidation pathway primarily contributed to MCFA production, and was inhibited under TAN stress. Functional populations likely survived TAN stress through osmoprotectant generation and potassium uptake regulation to maintain osmotic pressure, with NADH-ubiquinone oxidoreductase potentially compensating for ATP loss. This study enhances understanding of MCFA biosynthesis under TAN stress, aiding MCFA production system stability and efficiency improvement.

[Evaluation of the reporting quality of randomized controlled trials of acupuncture for depression based on CONSORT statement, STRICTA criteria and SHARE checklist].

OBJECTIVE: To evaluate the reporting quality of randomized controlled trials (RCTs) of acupuncture for depression. METHODS: Systematic searches were performed in PubMed, the Cochrane Library, EMbase, CNKI, Wanfang, SinoMed and VIP Database for RCTs of acupuncture in treatment of depression. The search time was from the establishment of database to December 1, 2023, and the language restriction was Chinese and English. The reporting quality of RCTs of acupuncture for depression was evaluated using the CONSORT statement, the international standardization for trial reporting, STRICTA, the international standard for clinical trial interventions of acupuncture, and SHARE, the guideline and checklist for reporting sham acupuncture controls. RESULTS: According to the CONSORT statement items, the items with the reporting rate less than 50% was accounted for 54.05% of all of the items for Chinese articles, and there were 8 and 1 items with a reporting rate of 0% and 100%, respectively. For the English articles, the items with the reporting rate less than 50% was accounted for 35.14% of all of the items, and there were 3 and 7 items with a reporting rate of 0% and 100%, respectively. The reporting rate of 15 items in Chinese and English articles was greater than 50%, e.g. structured abstract, background and purpose. Based on STRICTA criteria, the reporting rate of either Chinese or English articles was relatively high. The items for Chinese articles with the reporting rate less than 50% was accounted for 23.53% of all of the items, and there were 1 and 4 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 11.76% of all of the items, and there was 1 item with a reporting rate of either 0% or 100%. In compliance with SHARE checklist, the reporting rate was low for either Chinese or English articles. The items with the reporting rate less than 50% was accounted for 57.89% of all of the items for Chinese articles, and there were 2 and 0 items with a reporting rate of 0% and 100%, respectively. For English articles, the items with the reporting rate less than 50% was accounted for 52.63% of all of the items, and there was 1 item with a reporting rate of 0% and 100%, respectively. CONCLUSION: The overall reporting quality of RCTs of acupuncture for depression is low currently. It is urgent to enhance the reporting of the details on sham acupuncture control especially. It is suggested that RCTs should be reported strictly in compliance with the CONSORT statement, STRICTA criteria, and SHARE checklist in the future.

The association between online learning, perceived parental relationship, anxiety, and depression symptoms among secondary school students: insight from symptom network and cross-lagged panel network approach.

INTRODUCTION: Anxiety and depression often co-occur in adolescents, with factors from family and school playing a significant role in the comorbidity. However, network analysis has not examined and clarified the detailed bridge and central symptoms of this comorbidity caused by online learning and perceived parental relationships across different COVID-19 times. METHODS: Over four months, 2,356 secondary school students completed the Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7. Participants were divided into harmonious and disharmonious groups based on their answers to a question about parental conflicts. RESULTS: The results indicated that adolescents perceiving more parental conflicts showed a denser comorbidity network after four months of online learning. Significant bridge symptoms decreased from three to two across two waves in the harmonious group, while in the disharmonious group, they increased from two to three. The number of central symptoms increased from one in wave 1 to three in wave 2 for the harmonious group, while four in wave 1 decreased to two in wave 2 for the disharmonious group. Furthermore, the CLPN analysis revealed that the strongest positive cross-lagged edge intensity between symptoms was anhedonia-energy in the harmonious group, with anhedonia being the most trigger symptom. In contrast, for the disharmonious group, guilt-suicide and trouble relaxing-excessive worry were the strongest cross-lagged edge, and trouble relaxing was the most trigger symptom. CONCLUSION: These findings may have implications for interventions designed to promote adolescent mental health in the context of online learning and parental conflicts.

Machine Learning Models Reliably Predict Clinical Outcomes in Medial Patellofemoral Ligament Reconstruction.

PURPOSE: To develop the machine learning model to predict clinical outcomes following MPFLR and identify the important predictive indicators. METHODS: This study included patients who underwent MPFLR from January 2018 to December 2022. The exclusion criteria were as follows: 1) concurrent bony procedures, 2) history of other knee surgeries, and 3) follow-up period of less than 12 months. Forty-two predictive models were constructed for seven clinical outcomes (failure to achieve MCID of clinical scores, return to pre-injury sports, pivoting sports, and recurrent instability) using six machine learning algorithms (Random Forest, Logistic Regression, Support Vector Machine, Decision Tree, implemented multilayer perceptron, and K-nearest neighbor). The performance of the model was evaluated using metrics such as the area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. Additionally, Shapley Additive Explanation summary plot was employed to identify the important predictive factors of the best-performing model. RESULTS: A total of 218 patients met criteria. For the best-performing models in predicting failure to achieve the MCID for Lysholm, IKDC, Kujala, and Tegner scores, the AUCs and accuracies were 0.884 (good) and 87.3%, 0.859 (good) and 86.2%, 0.969 (excellent) and 97.0%, and 0.760 (fair) and 76.8%, respectively; 0.952 (excellent) and 95.2% for return to pre-injury sports; 0.756 (fair) and 75.4% for return to pivoting sports; and 0.943 (excellent) and 94.9% for recurrent instability. Low preoperative Tegner score, shorter time to surgery, and absence of severe trochlear dysplasia were significant predictors for return to pre-injury sports, while absence of severe trochlear dysplasia and patellar alta were significant predictors for return to pivoting sports. Older age, female sex, and low preoperative Lysholm score were highly predictive of recurrent instability. CONCLUSION: The predictive models developed using machine learning algorithms can reliably forecast the clinical outcomes of MPFLR, particularly demonstrating excellent performance in predicting recurrent instability. LEVEL OF EVIDENCE: Level III, case-control study.

Elucidation of the mechanism underlying the sequential catalysis of inulin by fructotransferase.

Glycoside hydrolase family 91 (GH91) inulin fructotransferase (IFTases) enables biotransformation of fructans into sugar substitutes for dietary intervention in metabolic syndrome. However, the catalytic mechanism underlying the sequential biodegradation of inulin remains unelusive during the biotranformation of fructans. Herein we present the crystal structures of IFTase from Arthrobacter aurescens SK 8.001 in apo form and in complexes with kestose, nystose, or fructosyl nystose, respectively. Two kinds of conserved noncatalytic binding regions are first identified for IFTase-inulin interactions. The conserved interactions of substrates were revealed in the catalytic center that only contained a catalytic residue E205. A switching scaffold was comprised of D194 and Q217 in the catalytic channel, which served as the catalytic transition stabilizer through side chain displacement in the cycling of substrate sliding in/out the catalytic pocket. Such features in GH91 contribute to the catalytic model for consecutive cutting of substrate chain as well as product release in IFTase, and thus might be extended to other exo-active enzymes with an enclosed bottom of catalytic pocket. The study expands the current general catalytic principle in enzyme-substrate complexes and shed light on the rational design of IFTase for fructan biotransformation.

The variation of acrylamide and 5-hydroxymethylfurfural in tea with different roasting degrees and the effects of tea polyphenols on their formation.

BACKGROUND: Roasting is an essential step in making roasted teas, and its role in producing flavors has been widely studied. However, the variation of potential hazardous compounds during the tea roasting process is still vague. The present study established an effective method based on liquid chromatography-triple quadrupole-tandem mass spectrometry to simultaneously determine the variation of acrylamide (AA), 5-hydroxymethylfurfural (5-HMF), and free amino acids during the tea roasting process. Meanwhile, the effects of several tea polyphenols on the formation of AA and 5-HMF were investigated by a wet-to-dry thermal model reaction. RESULTS: Medium-temperature roasted teas had the highest levels of AA and 5-HMF, with ranges of 0.13-0.15 µg g-1 and 68.72-123.98 µg g-1, respectively. Quantitative results showed that the levels of monosaccharides and amino acids decreased during roasting, which might contribute to the formation of 5-HMF and AA. Meanwhile, the decrease of epigallocatechin gallate (EGCG), epigallocatechin (EGC), and epicatechin (EC) might be related to their inhibitory effects on 5-HMF and AA. Thermal model reaction results showed that EGCG and EC significantly inhibited 5-HMF formation with a decline rate of 33.33% and 72.22%, respectively, mainly by trapping glucose. Gallic acid (GA) also had an inhibitory effect on the formation of AA (decreased by 92.86%) and 5-HMF (44.44%), mainly through impeding the preliminary reaction of asparagine and glucose. CONCLUSION: The roasting temperature determined the levels of AA and 5-HMF in teas. Catechins inhibited the formation of 5-HMF and AA mostly through trapping monosaccharides, while the inhibitory effect of GA was achieved by impeding the reaction. © 2024 Society of Chemical Industry.

Research on triaxial compressive mechanical properties and damage constructive model of post-thawing double-fractured quasi-sandstones with different angles.

Joints and fractures lead to different failure mechanisms in rock masses under different environments. The mechanical properties and failure mechanisms of rocks with fissures are key problems in rock mass engineering. Parallel double-fracture quasi-sandstone specimens with different dip angles were prepared and subjected to triaxial compression tests after a single freeze-thaw cycle. Pore development, crack propagation, damage evolution, and failure characteristics were analysed. Combined with the strength distribution theory of microelements and the static elastic modulus theory, a damage constitutive model of double-fracture quasi-sandstone under freeze-thaw cycles and loads was established. This study explored the pore development, fracture propagation, damage evolution, and failure characteristics of fractured sandstone after thawing. The results showed that the compression wave velocity of the thawed specimens decreased, the nuclear magnetic resonance (NMR) T2 curve shifted to the right, and the frost heave force promoted the development of the internal porosity in the specimens. With an increase in the crack dip angle, peak stress, expansion stress, cohesion and internal friction angle, the specimen showed a 'U' shaped change trend, compression cracks, and rock bridge penetration rate after failure decreased, and mixed failure of tension and shear gradually changed into shear failure. When the dip angles were 30° and 60°, the double fractured quasi-sandstone had larger total damage and more obvious brittle failure characteristics.

Prescribed performance adaptive neural event-triggered control for switched nonlinear cyber-physical systems under deception attacks.

In this paper, the design of an adaptive neural event-triggered control scheme for a class of switched nonlinear systems affected by external disturbances and deception attacks is presented. In order to address the effects caused by unknown disturbances, a switched nonlinear disturbance observer is used, and the error between the estimated signals and actual disturbances is small. Meanwhile, a prescribed performance function is introduced, which aims to ensure system output reaches the performance bounds within a predefined finite time. In addition, a dynamic event-triggered mechanism is designed to reduce the communication load. Based on the theoretical analysis, all signals within the closed-loop system are bounded, while simultaneously ensuring the complete elimination of Zeno behavior. Finally, the validity and efficacy of the scheme are proven by an example of numerical simulation.

Breakthrough of Hypoxia Limitation by Tumor-Targeting Photothermal Therapy-Enhanced Radiation Therapy.

Purpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers. Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity. Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors. Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.

Recent advancement of sonogenetics: A promising noninvasive cellular manipulation by ultrasound.

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation techniques. Sonogenetics, a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells, is gaining prominence along with optogenetics, electrogenetics, and magnetogenetics. Upon stimulation with ultrasound, these proteins trigger a cascade of cellular activities and functions. Unlike traditional ultrasound modalities, sonogenetics offers enhanced spatial selectivity, improving precision and safety in disease treatment. This technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications, including neuromodulation, oncologic treatments, stem cell therapy, and beyond. Although current literature predominantly emphasizes ultrasonic neuromodulation, this review offers a comprehensive exploration of sonogenetics. We discuss ultrasound properties, the specific ultrasound-sensitive proteins employed in sonogenetics, and the technique's potential in managing conditions such as neurological disorders, cancer, and ophthalmic diseases, and in stem cell therapies. Our objective is to stimulate fresh perspectives for further research in this promising field.