Trojan-horse inspired nanoblaster: X-ray triggered spot attack on radio-resistant cancer through radiodynamic therapy.

Radiotherapy as a mainstay of in-depth cervical cancer (CC) treatment suffers from its radioresistance. Radiodynamic therapy (RDT) effectively reverses radio-resistance by generating reactive oxygen species (ROS) with deep tissue penetration. However, the photosensitizers stimulated by X-ray have high toxicity and energy attenuation. Therefore, X-ray responsive diselenide-bridged mesoporous silica nanoparticles (DMSNs) are designed, loading X-ray-activated photosensitizer acridine orange (AO) for spot blasting RDT like Trojan-horse against radio-resistance cervical cancer (R-CC). DMSNs can encapsulate a large amount of AO, in the tumor microenvironment (TME), which has a high concentration of hydrogen peroxide, X-ray radiation triggers the cleavage of diselenide bonds, leading to the degradation of DMSNs and the consequent release of AO directly at the tumor site. On the one hand, it solves the problems of rapid drug clearance, adverse distribution, and side effects caused by simple AO treatment. On the other hand, it fully utilizes the advantages of highly penetrating X-ray responsive RDT to enhance radiotherapy sensitivity. This approach results in ROS-induced mitochondria damage, inhibition of DNA damage repair, cell cycle arrest and promotion of cancer cell apoptosis in R-CC. The X-ray responsive DMSNs@AO hold considerable potential in overcoming obstacles for advanced RDT in the treatment of R-CC.

Heterometallic Molecular and Ionic Isomers.

Numerous descriptions of structural isomerism in metal complexes do not list any molecular vs ionic isomers. At the same time, one of the most striking examples of structural isomerism in organic chemistry is molecular urea, which has the same atomic composition as the chemically distinct ionic ammonium cyanate. This iconic organic couple now meets its inorganic heterometallic counterpart. We introduce a new class of structural isomers, molecular vs ionic, that can be consummated in complex and coordinatively unsaturated polynuclear/heterometallic compounds. We report inorganic molecular and ionic isomers of the composition [NaCrFe (acac)3(hfac)3] (acac = acetylacetonate; hfac = hexafluoroacetylacetonate). Heterometallic molecular [CrIII(acac)3-Na-FeII(hfac)3] (1m) and ionic {[CrIII(acac)3-Na-CrIII(acac)3]+[FeII(hfac)3-Na-FeII(hfac)3]-} (1i) isomers have been isolated in pure form and characterized. While both ions are heterobimetallic trinuclear entities, the neutral counterpart is a heterotrimetallic trinuclear molecule. The two isomers exhibit distinctly different characteristics in terms of solubility, volatility, mass spectrometry ionization, and thermal behavior. Unambiguous assignment of the positions and oxidation/spin states of the Periodic Table neighbors, Fe and Cr, in both isomers have been made by a combination of characterization techniques that include synchrotron X-ray resonant diffraction, synchrotron X-ray fluorescence spectroscopy, Mössbauer spectroscopy, and DART mass spectrometry. The transformation between the two isomers that does take place in solutions of noncoordinating solvents has also been tested.

Photoresponse of Ti3C2Tx MXene promotes its adsorptive-reductive removal of Cr(VI) from water.

MXenes, such as Ti3C2Tx, demonstrate tremendous potential as heavy metal adsorbents due to their abundant reaction sites, high hydrophilicity, controllable interlayer spacing, and inherent reduction ability. However, their structural dependent pollutant removal performances and the related mechanisms are far less studied. Therefore, the removing abilities of Cr(VI) from water on Ti3C2Tx MXenes with different structures (multilayer (ML-) and delaminated (DL-) Ti3C2Tx) synthesized via several etching techniques were evaluated. Focusing on the most effective ML- and DL-Ti3C2Tx obtained by acid/fluoride salt etching, the impacts of structural variations on the Cr(VI) removal performances were explored. Both ML- and DL-Ti3C2Tx demonstrate outstanding Cr(VI) adsorption and reduction capabilities, achieving equilibrium within 500 min with capacities of 92.7 and 205 mg/g, respectively. The differences in removal mechanisms stemed from the varying adsorption and reduction capacities of two MXenes. ML-Ti3C2Tx, with lower surface area and porosity, had low adsorption capacity but superior reduction ability, efficiently converting most Cr(VI) to Cr(III) (66.8%). Conversely, DL-Ti3C2Tx exhibited better removal efficiency but a lower capacity for reduction (45.7%). Notably, although the partial reduction of DL-Ti3C2Tx to TiO2 results in its limited chemical reduction capacity, Ti3C2Tx might serve as a co-catalyst for TiO2, boosting the photoresponsiveness of DL-Ti3C2Tx or TiO2 through Ti3C2Tx/TiO2 heterojunctions, thereby facilitating photocatalysis to realize the reduction of Cr(VI). Both Ti3C2Tx exhibited both excellent Cr(VI) removal capacity and detoxification capacity, demonstrating their high potential in treating heavy metal pollutants in wastewater.

The Pivotal Role of Heavy Terpenes and Anthropogenic Interactions in New Particle Formation on the Southeastern Qinghai-Tibet Plateau.

Aerosol particles originating from the Qinghai-Tibet Plateau (QTP) readily reach the free troposphere, potentially affecting global radiation and climate. Although new particle formation (NPF) is frequently observed at such high altitudes, its precursors and their underlying chemistry remain poorly understood. This study presents direct observational evidence of anthropogenic influences on biogenic NPF on the southeastern QTP, near the Himalayas. The mean particle nucleation rate (J1.7) is 2.6 cm-3 s-1, exceeding the kinetic limit of sulfuric acid (SA) nucleation (mean SA: 2.4 × 105 cm-3). NPF is predominantly driven by highly oxygenated organic molecules (HOMs), possibly facilitated by low SA levels. We identified 1538 ultralow-volatility HOMs driving particle nucleation and 764 extremely low-volatility HOMs powering initial particle growth, with mean total concentrations of 1.5 × 106 and 3.7 × 106 cm-3, respectively. These HOMs are formed by atmospheric oxidation of biogenic precursors, unexpectedly including sesquiterpenes and diterpenes alongside the commonly recognized monoterpenes. Counterintuitively, over half of HOMs are organic nitrates, mainly produced by interacting with anthropogenic NOx via RO2+NO terminations or NO3-initiated oxidations. These findings advance our understanding of NPF mechanisms in this climate-sensitive region and underscore the importance of heavy terpene and NOx-influenced chemistry in assessing anthropogenic-biogenic interactions with climate feedbacks.

Genome-wide analysis of the ERF Family in Stephania japonica provides insights into the regulatory role in Cepharanthine biosynthesis.

Introduction: Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid (bisBIA) extracted from Stephania japonica, has received significant attention for its anti-coronavirus properties. While ethylene response factors (ERFs) have been reported to regulate the biosynthesis of various alkaloids, their role in regulating CEP biosynthesis remains unexplored. Methods: Genome-wide analysis of the ERF genes was performed with bioinformatics technology, and the expression patterns of different tissues, were analyzed by transcriptome sequencing analysis and real-time quantitative PCR verification. The nuclear-localized ERF gene cluster was shown to directly bind to the promoters of several CEP-associated genes, as demonstrated by yeast one-hybrid assays and subcellular localization assays. Results: In this work, 59 SjERF genes were identified in the S. japonica genome and further categorized into ten subfamilies. Notably, a SjERF gene cluster containing three SjERF genes was found on chromosome 2. Yeast one-hybrid assays confirmed that the SjERF gene cluster can directly bind to the promoters of several CEP-associated genes, suggesting their crucial role in CEP metabolism. The SjERFs cluster-YFP fusion proteins were observed exclusively in the nuclei of Nicotiana benthamiana leaves. Tissue expression profiling revealed that 13 SjERFs exhibit high expression levels in the root, and the qRT-PCR results of six SjERFs were consistent with the RNA-Seq data. Furthermore, a co-expression network analysis demonstrated that 24 SjERFs were highly positively correlated with the contents of various alkaloids and expression levels of CEP biosynthetic genes. Conclusion: This study provides the first systematic identification and analysis of ERF transcription factors in the S.japonica genome, laying the foundation for the future functional research of SjERFs transcription factors.

Evaluation of plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects.

BACKGROUND: Patients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging. METHODS: Here we retrospectively recruited seven families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned four groups. RESULTS: As expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these two groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis. CONCLUSION: Our study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.

Advances in targeted delivery of mRNA into immune cells for enhanced cancer therapy.

Messenger RNA (mRNA) therapy has been applied to the treatment of various human diseases including malignant tumors. Increasing evidences have shown that mRNA can enhance the efficacy of cancer immunotherapy by modulating the functions of immune cells and stimulating their activity. However, mRNA is a type of negatively charged biomacromolecules that are susceptible to serum nucleases and cannot readily cross the cell membrane. In the past few decades, various nanoparticles (NPs)-based delivery systems have been rationally designed and developed to facilitate the intracellular uptake and cytosolic delivery of mRNA. More importantly, by means of the specific recognition between the targeting ligands decorated on NP surface and receptors specifically expressed on immune cells, these mRNA delivery systems could be functionalized to target immune cells to further enhance the mRNA-based cancer immunotherapy. In this review, we briefly introduced the advancements of mRNA in cancer therapy, discussed the challenges faced by mRNA delivery, and systematically summarized the recent development in NPs-based mRNA delivery systems targeting various types of immune cells for cancer immunotherapy. The future development of NPs-mediated targeted mRNA delivery and their challenges in clinical translation are also discussed.

The Study of PIK3CA Hotspot Mutations and Co-Occurring with EGFR, KRAS, and TP53 Mutations in Non-Small Cell Lung Cancer.

Objective: PIK3CA-mutant non-small-cell lung cancer (NSCLC) is associated with other genetic mutations and may influence treatment strategies and clinical outcomes. We aimed to characterize PIK3CA mutations co-occurring with several major driver mutations using data from published cohorts and our medical center. Materials and Methods: We analyzed NSCLC patients harboring PIK3CA mutations from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering (MSK) databases and retrospectively identified NSCLC patients with PIK3CA-mutants at a single medical center from our electronic records. The Log rank test was used to determine the association between PIK3CA mutations and overall survival (OS) in NSCLC patients. Results: Common hotspot mutations in PIK3CA were found in exon 9 (c.1633G > A, E545K, and c.1624G > A, E542K) and exon 20 (c.3140A > G, H1047R) in all cohorts. Co-occurring mutations of PIK3CA with EGFR, KRAS, and TP53 have been frequently observed in patients with NSCLC, with different percentages in these datasets generated by different background. PIK3CA mutations were observed to be significantly associated with poor OS in lung adenocarcinomas patients in the MSKCC cohort (hazard ratio [HR] = 0.519, 95% confidence interval [CI] = 0.301-0.896; P <0.05). Conclusion: PIK3CA co-occurring mutations in other genes may represent distinct subsets of NSCLC. Further elucidation of the roles of PIK3CA hotspot mutations combined with other driver mutations, including EGFR and KRAS, is needed to guide effective treatment in patients with advanced NSCLC.

[Pharmacoeconomic evaluation of Shaoma Zhijing Granules in treatment of tic disorders in children].

This study conducted a pharmacoeconomic evaluation of Shaoma Zhijing Granules in the treatment of tic disorder(TD) in children. Firstly, from the perspective of the healthcare system, cost-effectiveness analysis was used to evaluate the economic efficiency of Shaoma Zhijing Granules compared with Changma Xifeng Tablets and Jiuwei Xifeng Granules in the treatment of TD in children. Then, through network Meta-analysis, the overall effectiveness of different regimens was calculated, combined with the total cost of the regimens, to calculate the incremental cost-effectiveness ratio(ICER). Finally, sensitivity analysis was performed to verify the stability of the study results and the credibility of the conclusions. This study included 17 articles, including 9 articles on Chinese patent medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 4 on Changma Xifeng Tablets), for the treatment of TD in children, and 8 articles on Chinese patent medicines combined with conventional western medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 3 on Changma Xifeng Tablets). In the Chinese patent medicine group, the total cost of Shaoma Zhijing Granules for treating TD was CNY 4 410.00, with clinical total effective rate of 77.53%; the total cost of Jiuwei Xifeng Granules for treating TD was CNY 5 192.70, with clinical total effective rate of 82.13%. The ICER of Jiuwei Xifeng Granules vs Shaoma Zhijing Granules was 169.95, higher than the willingness-to-pay(WTP, cost of increasing efficiency by 1% is CNY 85.70). Therefore, Jiuwei Xifeng Granules did not have a cost-effectiveness advantage over Shaoma Zhijing Granules. The total cost of Changma Xifeng Tablets for treating TD was CNY 1 282.50, with clinical total effective rate of 80.60%. The total cost of Changma Xifeng Tablets was lower and clinical total effective rate was higher than that of Shaoma Zhijing Granules. Overall, Shaoma Zhijing Granules did not have a cost-effectiveness advantage. In the Chinese patent medicine combined with conventional western medicine group, the total cost of Shaoma Zhijing Granules for treating TD + conventional western medicines was CNY 6 768.52/6 778.48, with clinical total effective rate of 96.18%. The total cost of Jiuwei Xifeng Granules + conventional western medicines for treating TD was CNY 6 522.56, with clinical total effective rate of 88.30%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Jiuwei Xifeng Granules + conventional western medicines was 31.20, lower than WTP. Therefore, Shaoma Zhijing Granules + conventional western medicines had a cost-effectiveness advantage over Jiuwei Xifeng Granules + conventional western medicines. The total cost of Changma Xifeng Tablets + conventional western medicines for treating TD was CNY 1 706.12, with clinical total effective rate of 95.39%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Changma Xifeng Tablets + conventional western medicines was 6 334.06, higher than WTP. Therefore, although Shaoma Zhijing Granules + conventional western medicines had higher clinical total effective rate compared with Changma Xifeng Tablets + conventional western medicines, it did not have a cost-effectiveness advantage. Overall, for different medication regimens(Chinese patent medicines monotherapy or in combination with conventional western medicines), Shaoma Zhijing Granules and Jiuwei Xifeng Granules both had a cost-effectiveness advantage, but compared with Changma Xifeng Tablets, neither had a cost-effectiveness advantage. For Chinese patent medicines in combination with conventional western medicines, clinical total effective rate of Shaoma Zhijing Granules in combination with conventional western medicines for the treatment of TD in children was the highest.

Re-examination of the Claimed Isolation of Stable Noncyclic 1,2-Disulfoxides.

Re-examination of the claimed isolation and X-ray characterization of di-p-tolyl and dimesityl 1,2-disulfoxides from thermolysis of the corresponding aryl sulfinimines and thiosulfinates showed that the isolated disulfide dioxides are instead the well-known isomeric thiosulfonates, as confirmed by XAS, DART-MS, X-ray, IR and NMR methods. Concerns with the original X-ray structures are addressed. Our results agree with the DFT prediction of very weak diaryl 1,2-disulfoxide S-S bond dissociation enthalpies. For now, room-temperature-stable noncyclic 1,2-disulfoxides remain unknown.

How the interplay of monitoring-enabled digital technologies and human factors facilitates or hinders metro systems' resilient response to operational disruptions.

The metro is susceptible to disruption risks and requires a system response capability to build resilience to manage disruptions. Achieving such resilient response state requires readiness in both the technology side, e.g., utilizing digital technologies (DTs) to monitor system components, and the human factors side, e.g., fostering positive human coping capabilities; however, these two sides are usually considered independently, without sufficient integration. This paper aims to develop and empirically test a model in which monitoring-enabled DTs, employees' reactions, and their positive capabilities are simultaneously considered in terms of their interplay and impact on system response capability. The results showed that while DTs for monitoring physical components enhanced perceived management commitment and fostered collective efficacy, DTs for monitoring human components increased psychological strain and inhibited improvisation capability, creating a "double-edged sword" effect on system response capability. Additionally, explicit management commitment buffered the adverse effect of DTs-induced psychological strain on individual improvisation.

Regulation of Biomineralization and Autophagy by the Stress-Sensing Transcription Factor CgRunx1 in Crassostrea gigas Under Daylight Ultraviolet B Radiation.

As human activities increase and environmental changes persist, increased ultraviolet B (UVB) radiation in aquatic ecosystems poses significant threats to aquatic life. This study, through transcriptomic analysis of the mantle tissue of Crassostrea gigas following UVB radiation exposure, identified and validated two key transcription factors, CgRunx1 and CgCBFß. The highest expression levels of CgRunx1 and CgCBFß in the mantle suggest their pivotal roles in this tissue. Co-immunoprecipitation experiments revealed that CgRunx1 and CgCBFß could form heterodimers and interact with each other. Furthermore, this study assessed the impact of UVB radiation on the levels of reactive oxygen species of the C. gigas, speculating that CgRunx1, as a potential redox-sensitive transcription factor, might be regulated by intracellular ROS. Through screening and binding site prediction analysis of target genes, coupled with dual-luciferase reporter assays, we verified that CgRunx1 might participate in regulating the biomineralization and autophagy processes in C. gigas by activating the transcriptional expression of target genes Transport and Golgi organization 1 and V-type proton ATPase catalytic subunit A. These findings provide new insights into the molecular response mechanisms of the C. gigas to UVB radiation and lay an important foundation for studying the adaptive evolution of bivalves to environmental stress.

The Burden and Clinical Features of Neovascular Glaucoma in A Major Tertiary Care Center in China.

PRCIS: This research presents the burden and clinical characteristics of NVG in Zhongshan Ophthalmic Center, employing the most extensive sample size and the longest uninterrupted temporal duration so far, which may provide a theoretical reference for the effective prevention and diagnosis of NVG. PURPOSE: To summarize the burden and clinical characteristics of neovascular glaucoma (NVG) in a major tertiary care center in China. METHODS: The clinical data of NVG patients in Zhongshan Ophthalmic Center (ZOC) between 2012 and 2021 were collected retrospectively, including their age, sex, affected eye, best-corrected visual acuity (BCVA), intraocular pressure (IOP), clinical stage and aetiology. RESULTS: In this study, we included 1877 eyes of 1749 patients who developed NVG, with 2.01:1 ratio of male to female. Their mean age was 53.14±16.69 years and those aged 41-70 years (65.2%) were most affected. Monocular patients were more predominant in most of them (92.7%), while 7.3% were binocular and 1667 eyes (88.8%) were at the angle­closure stage. The BCVA and IOP were 2.42±0.70 logMAR and 38.6±12.2 mmHg, respectively. Over the decade, the number of NVG patients and the proportion of NVG patients among glaucoma patients showed an increasing trend, with annual percentage changes (APCs) of 9.1% (95% CI: 5.0-13.3%, P=0.001) and 4.8% (95% CI: 2.2-7.4%, P=0.003), respectively. The top three primary conditions were diabetic retinopathy (DR), retinal vein occlusion (RVO), and retinal detachment (RD). Moreover, the APCs for the constituent ratio of DR and RVO were 4.4% (95% CI: 0.5-8.4%, P=0.031) and ï¹£4.6% (95% CI: ï¹£8.4% to ï¹£0.7%, P=0.028), respectively. However, the first and second causes of NVG in minors (<18 years old) were Coat's disease and ocular tumours, followed by RD and RVO in third place. The top cause of NVG in patients aged 65 years and older was RVO. CONCLUSIONS: The burden of NVG is increasing, emphasizing the need to improve preventive strategies focusing on primary diseases such as DR, RVO, and RD, particularly the increasing proportion of DR cases and the previously underemphasized RD patients, while also highlighting the differences in primary diseases across different age groups.

Exercise Alleviates Cardiovascular Diseases by Improving Mitochondrial Homeostasis.

Engaging in regular exercise and physical activity contributes to delaying the onset of cardiovascular diseases (CVDs). However, the physiological mechanisms underlying the benefits of regular exercise or physical activity in CVDs remain unclear. The disruption of mitochondrial homeostasis is implicated in the pathological process of CVDs. Exercise training effectively delays the onset and progression of CVDs by significantly ameliorating the disruption of mitochondrial homeostasis. This includes improving mitochondrial biogenesis, increasing mitochondrial fusion, decreasing mitochondrial fission, promoting mitophagy, and mitigating mitochondrial morphology and function. This review provides a comprehensive overview of the benefits of physical exercise in the context of CVDs, establishing a connection between the disruption of mitochondrial homeostasis and the onset of these conditions. Through a detailed examination of the underlying molecular mechanisms within mitochondria, the study illuminates how exercise can provide innovative perspectives for future therapies for CVDs.

Birdlike broadband neuromorphic visual sensor arrays for fusion imaging.

Wearable visual bionic devices, fueled by advancements in artificial intelligence, are making remarkable progress. However, traditional silicon vision chips often grapple with high energy losses and challenges in emulating complex biological behaviors. In this study, we constructed a van der Waals P3HT/GaAs nanowires P-N junction by carefully directing the arrangement of organic molecules. Combined with a Schottky junction, this facilitated multi-faceted birdlike visual enhancement, including broadband non-volatile storage, low-light perception, and a near-zero power consumption operating mode in both individual devices and 5 × 5 arrays on arbitrary substrates. Specifically, we realized over 5 bits of in-memory sensing and computing with both negative and positive photoconductivity. When paired with two imaging modes (visible and UV), our reservoir computing system demonstrated up to 94% accuracy for color recognition. It achieved motion and UV grayscale information extraction (displayed with sunscreen), leading to fusion visual imaging. This work provides a promising co-design of material and device for a broadband and highly biomimetic optoelectronic neuromorphic system.

Synthesis and Evaluation of 18F-Labeled Phenylpiperazine-like Dopamine D3 Receptor Radioligands for Positron Emission Tomography Imaging.

The dopamine D3 receptor (D3R) is important in the pathophysiology of various neuropsychiatric disorders, such as depression, bipolar disorder, schizophrenia, drug addiction, and Parkinson's disease. Positron emission tomography (PET) with innovative radioligands provides an opportunity to assess D3R in vivo and to elucidate D3R-related disease mechanisms. Herein, we present the synthesis of eight 18F-labeled phenylpiperazine-like D3R-selective radioligands possessing good radiochemical purity (>97%), in vitro stability (>95%), and befitting lipophilicity. Based on in vitro binding assays and static microPET studies, the phenylpiperazine-like radioligands [18F]FBPC01 and [18F]FBPC03 were chosen as lead radioligands targeting D3R. Molecular docking further elucidated their binding mechanism. Radiolabeling conditions were optimized and then applied to an automated radiolabeling process, affording products with high specific activity (>112 GBq/µmol). Dynamic rat PET study demonstrated the specific binding of [18F]FBPC01 and [18F]FBPC03 to D3R in the brain ventricles and the pituitary gland. Validated by dynamic PET data analysis, biodistribution study, and metabolism analysis, [18F]FBPC03 exhibited the highest PET signal-to-noise ratio, good D3R-specific binding in the brain ventricles and pituitary gland of rats with few off-target binding, negligible defluorination, and stable brain metabolism, which indicated that [18F]FBPC03 was a promising D3R radioligand.

Beyond skin deep: Revealing the essence of iPS cell-generated skin organoids in regeneration.

Various methods have been used for in vivo and in vitro skin regeneration, including stem cell therapy, tissue engineering, 3D printing, and platelet-rich plasma (PRP) injection therapy. However, these approaches are rooted in the existing knowledge of skin structures, which overlook the normal physiological processes of skin development and fall short of replicating the skin's regenerative processes outside the body. This comprehensive review primarily focuses on skin organoids derived from human pluripotent stem cells, which have the capacity to regenerate human skin tissue by restoring the embryonic skin structure, thus offering a novel avenue for producing in vitro skin substitutes. Furthermore, they contribute to the repair of damaged skin lesions in patients with systemic sclerosis or severe burns. Particular emphasis will be placed on the origins, generations, and applications of skin organoids, especially in dermatology, and the challenges that must be addressed before clinical implementation.

[Influence of Tis108 on GA content and expression of key enzyme GeCYP714A1 involved in GA deactivation of Gastrodia elata].

To investigate the influence of the strigolactone inhibitor Tis108 on the growth of Gastrodia elata, this study treated G. elata tuber with Tis108 solution of 10 µmol·L~(-1) and measured the content of endogenous hormone gibberellin(GA) in the tuber. By using reverse transcription-polymerase chain reaction(RT-PCR) technology, the key enzyme GeCYP714A1 gene involved in GA deactivation was cloned. Bioinformatics analysis on the GeCYP714A1 gene was carried out by using ExPASy, SWISS-MODEL, MEGA, etc., and its expression levels in different parts of G. elata were determined. The results showed that after Tis108 treatment, GA content in G. elata tuber was significantly increased, and the transcription level of the GeCYP714A1 gene was significantly decreased. The full length of the coding region of the GeCYP714A1 gene is 1 173 bp, encoding 390 amino acids. The protein has a molecular weight of 44.85 kDa, a theoretical isoelectric point of 9.83, an instability index of 49.20, an aliphatic index of 89.03, and a grand average of hydropathicity of-0.235, classifying it as an unstable, basic, hydrophilic protein, and the GeCYP714A1 protein was localized in the mitochondria, lacking a signal peptide and a transmembrane structure. Phylogenetic tree analysis revealed that GeCYP714A1 was most closely related to the DcCYP714C2(PKU78454.1) protein from Dendrobium candidum, with a sequence identity of 67.25%. The qRT-PCR analysis of the expression patterns of the GeCYP714A1 gene indicated that GeCYP714A1 had the highest transcription level in G. elata tuber, followed by stem and inflorescence. The study represented that Tis108 inhibited the transcription level of GeCYP714A1 involved in GA deactivation in G. elata tuber, thereby increasing the accumulation of GA and affecting the growth of G. elata tuber. These results provided a basis for further studies of strigolactone regulation of GA signal and tuber development in G. elata.

Machine-Learning-Assisted Design of Deep Eutectic Solvents Based on Uncovered Hydrogen Bond Patterns.

Non-ionic deep eutectic solvents (DESs) are non-ionic designer solvents with various applications in catalysis, extraction, carbon capture, and pharmaceuticals. However, discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES formation. The search for DES relies heavily on intuition or trial-and-error processes, leading to low success rates or missed opportunities. Recognizing that hydrogen bonds (HBs) play a central role in DES formation, we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning (ML) models to discover new DES systems. We first analyze the HB properties of 38 known DES and 111 known non-DES systems using their molecular dynamics (MD) simulation trajectories. The analysis reveals that DES systems have two unique features compared to non-DES systems: The DESs have ① more imbalance between the numbers of the two intra-component HBs and ② more and stronger inter-component HBs. Based on these results, we develop 30 ML models using ten algorithms and three types of HB-based descriptors. The model performance is first benchmarked using the average and minimal receiver operating characteristic (ROC)-area under the curve (AUC) values. We also analyze the importance of individual features in the models, and the results are consistent with the simulation-based statistical analysis. Finally, we validate the models using the experimental data of 34 systems. The extra trees forest model outperforms the other models in the validation, with an ROC-AUC of 0.88. Our work illustrates the importance of HBs in DES formation and shows the potential of ML in discovering new DESs.

Molecular biological mechanisms of radiotherapy-induced skin injury occurrence and treatment.

Radiotherapy-Induced Skin Injury (RISI) is radiation damage to normal skin tissue that primarily occurs during tumor Radiotherapy and occupational exposure. The risk of RISI is high due to the fact that the skin is not only the first body organ that ionizing radiation comes into contact with, but it is also highly sensitive to it, especially the basal cell layer and capillaries. Typical clinical manifestations of RISI include erythema, dry desquamation, moist desquamation, and ulcers, which have been established to significantly impact patient care and cancer treatment. Notably, our current understanding of RISI's pathological mechanisms and signaling pathways is inadequate, and no standard treatments have been established. Radiation-induced oxidative stress, inflammatory responses, fibrosis, apoptosis, and cellular senescence are among the known mechanisms that interact and promote disease progression. Additionally, radiation can damage all cellular components and induce genetic and epigenetic changes, which play a crucial role in the occurrence and progression of skin injury. A deeper understanding of these mechanisms and pathways is crucial for exploring the potential therapeutic targets for RISI. Therefore, in this review, we summarize the key mechanisms and potential treatment methods for RISI, offering a reference for future research and development of treatment strategies.