Site-Specific Stability Evaluation of Antibody-Drug Conjugate in Serum Using a Validated Liquid Chromatography-Mass Spectrometry Method.

Antibody-drug conjugate (ADC) consists of engineered antibodies and cytotoxic drugs linked via a chemical linker, and the stability of ADC plays a crucial role in ensuring its safety and efficacy. The stability of ADC is closely related to the conjugation site; however, no method has been developed to assess the stability of different conjugation sites due to the low response of conjugated peptides. In this study, an integrated strategy was developed and validated to assess the stability of different conjugation sites on ADC in serum. Initial identification of the conjugated peptides of the model drug ado-trastuzumab emtansine (T-DM1) was achieved by the proteomic method. Subsequently, a semiquantitative method for conjugated peptides was established in liquid chromatography-hybrid linear ion trap triple quadrupole mass spectrometry (LC-QTRAP-MS/MS) based on the qualitative information. The pretreatment method of the serum sample was optimized to reduce matrix interference. The method was then validated and applied to evaluate the stability of the conjugation sites on T-DM1. The results highlighted differences in stability among the different conjugation sites on T-DM1. This is the first study to assess the stability of different conjugation sites on the ADC in serum, which will be helpful for the design and screening of ADCs in the early stages of development.

Jieduquyuziyin prescription alleviates lupus development via inhibiting neddylation pathway to promote Bim-induced apoptosis of double negative T cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Jieduquyuziyin prescription (JP) is an empirical prescription approved for application to treat systemic lupus erythematosus (SLE) in hospital within China. Despite the prominent treatment effect of JP clinically, further investigation is imperative to explore its underlying mechanisms. AIM OF THE STUDY: We aim to investigate the impact of JP on DN T cell apoptosis in the treatment of SLE and the specific regulation mechanisms. MATERIALS AND METHODS: Firstly, female MRL/lpr mice were treated with JP and the therapeutic efficacy of JP was evaluated via skin lesions, lymphoid organ enlargement, accumulation of autoantibodies and renal function. Then, flow cytometer analysis was performed to evaluate the proportions and the apoptosis of T cell subpopulations. Based on the above results, double-negative (DN) T cells were subjected to proteomic with subsequent differential screening. The expression of Ube2m and Bim was further validated using real-time PCR and Western blot. Subsequently, DN T cells were incubated with JP-contained serum in vitro, and cell apoptosis was quantified using flow cytometry. Additionally, the expression levels of Ube2m, Bim and other associated proteins were also assessed through western blotting. To further clarify whether Ube2m serves as the key target of JP in regulating DN T cell apoptosis, the mice that Ube2m was specific deleted in T cells with spontaneous lupus (Ube2m-/-lpr) were utilized. JP was administered to WTlpr or Ube2m-/-lpr mice, followed by assessment of the lupus condition and DN T cell apoptosis. RESULTS: JP administration effectively ameliorated the lupus phenotype. Then flow cytometry assay showed that JP treatment enhanced DN T cell apoptosis to reduce their accumulation and restored the immune homeostasis. Proteomic analysis revealed a significant inhibition of Ube2m for JP treatment, which is essential for maintaining homeostasis of DN T cells. Further experiments confirmed that JP treatment effectively downregulated the expression of Ube2m and subsequently upregulated the level of pro-apoptotic protein Bim with decreased Bim degradation. In vitro experiments also confirmed that JP-contained serum significantly facilitated DN T cell apoptosis and reduced DN T cell accumulation by inhibiting Ube2m expression. Furthermore, Ube2m-/-lpr mice were utilized and the impact of JP treatment on the apoptosis of DN T cells was found to be minimal in the absence of Ube2m. Mechanistic investigation reveals that JP exerts its effects by suppressing the expression of Ube2m, subsequently inhibiting CRL-dependent degradation of Bim, and ultimately promoting Bim-induced apoptosis in DN T cells. Furthermore, the blockade of Ube2m in T cells effectively prevents JP-induced apoptosis in DN T cells, underscoring Ube2m as one crucial therapeutic target of JP in mediating DN T cell apoptosis and managing SLE. CONCLUSIONS: Our findings indicate that JP treatment effectively restores the homeostasis of DN T cells in SLE by inhibiting Ube2m expression, thereby reducing Bim ubiquitination degradation. This ultimately enhanced DN T cell apoptosis and alleviated lupus phenotype.

Evaluating the Feasibility of Cervical Vertebral Maturation Stages as an Alternative to Risser Sign in Assessing Skeletal Maturity in Adolescent Idiopathic Scoliosis Patients.

BACKGROUND: Radiographic methods for evaluating skeletal maturity traditionally include the Risser sign and the hand-wrist maturation method. While the cervical vertebral maturation (CVM) stage is widely recognized in orthodontics, its application in assessing spinal growth, particularly in adolescent idiopathic scoliosis (AIS), has been less explored. This study explores the correlation between CVM, chronological age, and the Risser sign to evaluate the feasibility of CVM in assessing skeletal development in adolescents. METHODS: This prospective study included adolescent idiopathic scoliosis (AIS) patients and asymptomatic adolescents, aged 7-15 years, who underwent full-spine imaging with clear visibility of the cervical and pelvic regions. The correlation between CVM and the Risser sign was analyzed. The height of the cervical C3-7 vertebral body was measured, and its growth trend with age was examined. Differences between AIS patients and asymptomatic adolescents were compared. RESULTS: A total of 85 AIS patients (mean age 11.44±2.36 years) and 47 asymptomatic adolescents (mean age 11.48±3.14 years) were included. No statistically significant differences were observed in age, Risser sign grading, CVM staging, or C3-7 vertebral body height between the two groups. Chronological age showed a stronger correlation with CVM stages than with the Risser sign in both the AIS group (r=0.93 vs. r=0.82, P<0.01) and the asymptomatic group (r=0.81 vs. r=0.72, P<0.01). CONCLUSIONS: The CVM stage, which shows a strong correlation with Risser sign grading, could serve as a reliable alternative for assessing skeletal maturity in adolescent subjects, particularly in clinical scenarios where minimizing radiation exposure is a priority.

Preparation of starch-based oral fast-disintegrating nanofiber mats for astaxanthin encapsulation and delivery via emulsion electrospinning.

Developing green and efficient delivery systems to promote bioavailability of bioactive ingredients is a sustained demand in food industry. In this work, the astaxanthin (AST)-loaded starch-based fast-dissolving nanofibers with core-shell structure were prepared by emulsion electrospinning technique without using any organic solvent. To load water-insoluble AST in hydrophilic octenyl succinic anhydride starch (OSAS)/polyvinyl alcohol (PVA) nanofiber matrices, AST-loaded nanoscale emulsions (212.19 ±â€¯5.63 nm) with high encapsulation efficiency (91.54 ±â€¯0.14 %) were prepared as a precursor for emulsion electrospinning, using OSAS/PVA aggregates as an emulsifier. The core-shell structure of nanofibers was revealed by the Transmission electron microscopy (TEM), with average diameter of 509.58 ±â€¯12.77 nm, and 88.64 ±â€¯0.49 % for AST were effectively encapsulated in core layer. Nanofiber mats exhibited high encapsulation efficiency (85.11 ±â€¯1.53 %) and excellent storage stability over 7 d. Meanwhile, amorphous transformation of AST enabled it possess higher water solubility, bioaccessibility, and antioxidant properties (97.72 ±â€¯2.17 %) than free AST in aqueous system. The results demonstrated that the green, nontoxic, and biodegradable nanofiber mats prepared by emulsion electrospinning successfully realized the encapsulation and delivery of AST, with broad application prospects in the food and pharmaceutical fields.

Does enterprise digital transformation contribute to green innovation? Micro-level evidence from China.

The synergy of digitalization and greening has emerged as a prominent means to achieve the goal of "carbon peaking and carbon neutrality". Given its significant contribution to carbon emissions, the impact of digital transformation on green innovation in manufacturing enterprises remains a longstanding research hotspot. Therefore, based on the data from China A-share listed manufacturing companies spanning from 2007 to 2022, this paper empirically analyzes the influence and mechanism of digital transformation on green innovation. Our findings reveal that digital transformation can significantly promote green innovation in manufacturing enterprises, with a particularly pronounced effect on substantive green innovation. These conclusions withstand rigorous robustness tests. Mechanism analysis shows that digital transformation can facilitate green innovation by improving internal control quality and fostering industry-university-research cooperation. Moreover, our moderation analysis reveals that both equity incentives and compensation incentives strengthen the positive relationship between digital transformation and green innovation in manufacturing enterprises. Heterogeneity analysis proves that digital transformation exerts a more pronounced impact on green innovation of state-owned manufacturing enterprises, non-heavily polluted manufacturing enterprises, and enterprises located in regions with strong intellectual property protection. Furthermore, the transformation of digital underlying technologies is more conducive to fostering green innovation compared to practical application transformation. Subsequent investigation into the economic and social effects of green innovation indicates that it effectively reduces pollution emissions from manufacturing enterprises without compromising their development. Additionally, the emission reduction and income-generating effect resulting from digital transformation primarily manifest through substantive green innovation. This research expands upon the theory regarding the impact of digital transformation on green innovation in micro-manufacturing enterprises, providing empirical support for facilitating low-carbon transformations among manufacturing enterprises under the goal of "carbon peaking and carbon neutrality".

Electromagnetically Induced Transparency Cooling of High-Nuclear-Spin Ions.

We report the electromagnetically induced transparency (EIT) cooling of ^{137}Ba^{+} ions with a nuclear spin of I=3/2, which are a good candidate of qubits for future large-scale trapped-ion quantum computing. EIT cooling of atoms or ions with a complex ground-state level structure is challenging due to the lack of an isolated Λ system, as the population can escape from the Λ system to reduce the cooling efficiency. We overcome this issue by leveraging an EIT pumping laser to repopulate the cooling subspace, ensuring continuous and effective EIT cooling. We cool the two radial modes of a single ^{137}Ba^{+} ion to average motional occupations of 0.08(5) and 0.15(7), respectively. Using the same laser parameters, we also cool all the ten radial modes of a five-ion chain to near their ground states. Our approach can be adapted to atomic species possessing similar level structures. It allows engineering of the EIT Fano-like spectrum, which can be useful for simultaneous cooling of modes across a wide frequency range, aiding in large-scale trapped-ion quantum information processing.

Abnormal thalamocortical network dynamics in patients with migraine and its relationship with electroacupuncture treatment response.

Acupuncture is an effective and safe alternative treatment to prevent and treat migraine, but its central analgesic mechanism remains poorly understood. It is believed that the dysfunction of the thalamocortical connectivity network is an important contributor to migraine pathophysiology. This study aimed to investigate the abnormal thalamocortical network dynamics in patients with migraine without aura (MWoA) before and after an 8-week electroacupuncture treatment. A total of 143 patients with MWoA and 100 healthy controls (HC) were included, and resting-state functional magnetic resonance imaging (fMRI) data were acquired. Dynamic functional network connectivity (dFNC) was calculated for each subject. The modulation effect of electroacupuncture on clinical outcomes of migraine, dFNC, and their association were investigated. In our results, dFNC matrices were classified into two clusters (brain states). As compared with the HC, patients with MWoA had a higher proportion of brain states with a strong thalamocortical between-network connection, implying an abnormal balance of the network organization across dFNC brain states. Correlation analysis showed that this abnormality was associated with summarized clinical measurements of migraine. A total of 60 patients were willing to receive an 8-week electroacupuncture treatment, and 24 responders had 50% changes in headache frequency. In electroacupuncture responders, electroacupuncture could change the abnormal thalamocortical connectivities towards a pattern more similar to that of HC. Our findings suggested that electroacupuncture could relieve the symptoms of migraine and has the potential capacity to regulate the abnormal function of the thalamocortical circuits.

Clinical features and prognostic biomarkers in patients with SMARCA4-mutated non-small cell lung cancer.

Background: Patients with non-small cell lung cancer (NSCLC) carrying SMARCA4 mutations (SMARCA4-Mut) tend to have more advanced disease and a poor prognosis. However, due to the rarity of this mutation and the lack of related studies, the characteristics of SMARCA4-Mut NSCLC patients remains poorly determined. To clarify the clinical characteristics and prognostic factors of SMARCA4-Mut NSCLC, we initiated the present study to provide a clinical reference. Methods: We used data from two cohorts of NSCLC-SMARCA4-mutated samples: The Cancer Genome Atlas (TCGA) database and our center's clinical data. The TCGA database was used to obtain 481 NSCLC-SMARCA4-Mut samples for clinical characterization. The center collected data on 224 consecutive NSCLC patients treated between December 2020 to July 2022. Among them, 26 harbored SMARCA4 mutations, and 20 were eligible for inclusion in the study. Clinical, pathological, and molecular features, as well as prognostic role of SMARCA4 mutations were analyzed. Additionally, we analyzed the prognostic impact of Napsin A expression in SMARCA4-Mut patients. Results: The TCGA database included 480 patients with SMARCA4-Mut NSCLC, 311 males (64.8%) and 169 females (35.2%), with a median age of 67 years. Among the 20 SMARCA4-Mut patients in our center series, 12 (60%) were males and 8 (40%) females, with a median age of 63. The intergroup prognostic correlation analysis showed that SMARCA4-Mut patients had significantly worse prognosis than those the wild-type SMARCA4 (SMARCA4-WT) (P=0.04). Within the SMARCA4-Mut group, patients with Napsin A expression had longer overall survival (OS) (P=0.03) than those without expression. Median survival in the Napsin A-positive and negative groups was 32 and 15 months, respectively. According to time-dependent receiver operating curve analysis, patients with Napsin A expression had significantly longer first-line treatment progression-free survival (PFS1) [area under the curve (AUC) =0.748] and OS (AUC =0.586). No prognostic value of Napsin A was found in patients SMARCA4-WT patients. Conclusions: SMARCA4-Mut is an adverse prognostic feature in NSCLC patients. Napsin A expression in SMARCA4-Mut patients is associated with prolonged OS.

LSPR-susceptible metasurface platform for spectrometer-less and AI-empowered diagnostic biomolecule detection.

In response to the growing demand for biomolecular diagnostics, metasurface (MS) platforms based on high-Q resonators have demonstrated their capability to detect analytes with smart data processing and image analysis technologies. However, high-Q resonator meta-atom arrays are highly sensitive to the fabrication process and chemical surface functionalization. Thus, spectrum scanning systems are required to monitor the resonant wavelength changes at every step, from fabrication to practical sensing. In this study, we propose an innovative dielectric resonator-independent MS platform that enables spectrometer-less biomolecule detection using artificial intelligence (AI) at a visible wavelength. Functionalizing the focused vortex MS to capture gold nanoparticle (AuNP)-based sandwich immunoassays causes the resulting vortex beam profiles to be significantly affected by the localized surface plasmon resonance (LSPR) occurring between AuNPs and meta-atoms. The convolutional neural network algorithm was carefully trained to accurately classify the AuNP concentration-dependent focused vortex beam, facilitating the determination of the concentration of the targeted diagnostic biomolecule. Successful in situ identification of various biomolecule concentrations was achieved with over 99 % accuracy, indicating the potential of combining an LSPR-susceptible MS platform and AI for continuously tracking various chemical and biological compounds.

Identification of bile acids in snake bile by hydrogen/deuterium exchange mass spectrometry and quantitative structure-retention relationship analysis.

Natural bile acids, a class of steroids with a valeric acid side chain at the C-17 position, present significant challenges in separation and analysis due to structural similarities, isomerism, and large polarity differences. Therefore, advanced analytical methods are essential for the accurate identification and quantification of bile acids. This study conducted a comprehensive qualitative analysis of bile acids by integrating liquid chromatography-tandem mass spectrometry (LC-MS/MS), hydrogen-deuterium exchange tandem mass spectrometry (HDX-MS/MS), and quantitative structure-retention relationship (QSRR) methods. Firstly, LC-MS/MS conditions were optimized to enhance chromatographic separation and improve the reliability of characteristic fragment ions. MS/MS fragmentation rules for bile acids were derived from the mass spectral data of bile acid standards and validated through HDX-MS/MS experiments. Secondly, potential bile acids in snake bile were identified based on these validated fragmentation rules, and a QSRR model was established to predict the retention times of the proposed structures. Thirdly, HDX-MS/MS was applied to assist in identifying bile acid isomers. Finally, a total of 150 bile acids, including 11 free bile acids (free BA), 5 glyco-bile acids (GBA) and 134 tauro-bile acids (TBA), were detected in snake bile. Thirteen bile acids were accurately characterized by comparing their retention time and MS/MS spectra with standards. Forty-nine bile acids were reasonably annotated using the QSRR model and HDX-MS/MS. This study is notable for being the first to utilize the QSRR and HDX-MS/MS techniques for the annotation of bile acids in snake bile, providing a robust framework for the structural elucidation of these compounds.

An expert consensus on managing dupilumab-related ocular surface disorders in people with atopic dermatitis 2024.

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin condition which affects all ages. New therapies, including the monoclonal antibody therapy dupilumab, offer excellent efficacy. However, in clinical trials, and emphasised in real-world observations, the unexpected increased frequency of ocular adverse effects became apparent. The effectiveness of dupilumab and the unpredictability of ocular adverse effects mean that clinicians need guidance on counselling patients prior to treatment and on managing them if they arise. OBJECTIVES: The British Association of Dermatologists (BAD) and Royal College of Ophthalmologists collaborated on this consensus guidance on managing dupilumab-related ocular surface disorders (DROSD). METHODS: A multidisciplinary group was formed of adult and paediatric dermatologists and ophthalmologists with DROSD expertise, patient representation, and BAD Clinical Standards Unit. A literature search was conducted, and the results reviewed. All recommendations were reviewed, discussed and voted on. RESULTS: The recommendations pertain to dermatology and ophthalmology management, and apply to all ages, unless otherwise stated. Importantly, initiation of dupilumab for AD should not be delayed for most eye disorders except acute new problems, e.g. infections, or potentially severe conditions, e.g. a history of corneal transplant (ophthalmology advice should be sought first). There is insufficient evidence to recommend lubricant drops prophylactically. Dermatologists should assess eye complaints to diagnose DROSD; a severity grading system is provided. DROSD management differs slightly in those aged <7 years as ocular complications may affect neuro-ocular development; therefore, irrespective of DROSD severity, this population should be referred for ophthalmology advice. In those aged ≥7 years, dermatologists should feel confident to trial treatment and reserve ophthalmology advice for severe or non-responding cases. Discussion about dupilumab withdrawal should be prompted by a significant impact on quality of life, threat to sight, or other complications. CONCLUSIONS: Although dupilumab is a highly effective agent for treating AD, the risk of ocular adverse effects should not inhibit clinicians or patients from using it, but clinicians should be aware of them. If a patient develops DROSD, there are clear pathways to assess severity and offer initial management; where ineffective, dermatologists should assess the urgency and seek advice from or initiate referral to ophthalmology. While the evidence reviewed for these guidelines reflects the extensive literature on dupilumab, we believe our advice has relevance for ocular surface disorders in atopic dermatitis (AD) patients treated with tralokinumab and lebrikizumab.

Timing mowing for maximal energy gain - Managing foraging habitat of wintering geese under extreme drought conditions.

The availability of high-quality food resources is a critical determinant of wildlife fitness. Over the past two decades, phenological mismatch - the temporal misalignment between animals' peak nutrient demand and optimal resource availability - has emerged as a significant conservation challenge. This issue is particularly worrisome for migratory birds, which must accumulate energy reserves to meet the elevated metabolic demands of migration between breeding and wintering grounds. In Poyang Lake, a crucial wintering ground along the East Asian-Australasian flyway, increasing asynchrony between vegetation growth and the migration of herbivorous waterbirds significantly impedes conservation efforts and presents a major management challenge for this Ramsar wetland. This study evaluates the efficacy of mowing, a grassland management measure, in regulating plant growth processes and restoring food resources for geese. In-situ mowing experiments were conducted with varying timings in Carex wet meadows, the primary foraging habitats of geese. Optimal mowing times were identified, and the maximum goose carrying capacity was assessed by comparing Carex growth and nutritional dynamics with goose dietary requirements. The results reveal that mowing effectively slows down the aging process of Carex, and protein content is identified as a critical limiting factor for geese foraging. Different mowing timings extend the suitable foraging period by 11-25 days. Estimates suggest varying carrying capacities with different mowing timings, supporting goose populations ranging from 133 to 2,046 in Changhuchi Lake during wintering. The optimal mowing window is early October, avoiding dates before late September and after late November. Moreover, multiple-stage mowing is recommended to accommodate different wintering stages. The study highlights mowing as a potential habitat restoration approach for goose conservation, effectively mitigating the challenges imposed by phenological mismatch directly and indirectly caused by anthropogenic activities.

Adjustable flanged technique for secondary implantation of four-point scleral­fixated posterior chamber intraocular lenses using two parallel 6-0 polyglactin sutures.

OBJECTIVE: To assess the efficacy and safety of using the adjustable flanged technique for secondary implantation of four-point scleral­fixated posterior chamber intraocular lenses with two parallel 6-0 polyglactin sutures. METHODS: Two parallel 6-0 polyglactin sutures were passed separately through the two haptics on the horizontal line of the 4-haptic IOL. The four externalized sutures were then trimmed and cauterized to form flanges. The best corrected visual acuity, intraocular pressure, and complications in all patients were observed and recorded. RESULTS: The flanged technique using two parallel 6-0 polyglactin sutures was applied to 14 aphakic eyes. The average preoperative best corrected visual acuity was 1.00 ± 0.88 LogMAR (Snellen 20/200), which improved to 0.42 ± 0.38 LogMAR (Snellen 20/48) at the final follow-up (P = 0.004). None of the patients experienced vitreous hemorrhage, low intraocular pressure, or issues with exposed or broken sutures. CONCLUSION: The simplicity of the technique, along with its ability to accommodate adjustments post-implantation, allows for optimal positioning and reduces risks like IOL tilt or dislocation. Overall, this is a promising approach to secondary IOL implantation, with potential benefits for both patient outcomes and surgical efficiency.

Combination of Metabolomics, Lipidomics, and Molecular Biology for the Investigation of the Metabolic Disturbance of Short-Term Administration of Emodin.

Emodin, a natural anthraquinone derivative, is an active ingredient in many Chinese traditional herbs. Interestingly, although it is generally considered to possess hepatoprotective activity, some studies have also reported that it has a certain degree of hepatotoxicity. Additionally, the underlying metabolic regulation of emodin remains uncertain. Therefore, we conducted a nontargeted metabolomic study based on UHPLC/Q-Orbitrap-MS and NMR. Data are available via ProteomeXchange with the identifier PXD055000. The results indicated a close association between the short-term administration of emodin and lipid metabolism. Moreover, a lipidomics investigation utilizing QTRAP 6500+ UHPLC-MS/MS was conducted, with a focus on determining the position of C═C double bonds in unsaturated lipids based on Paternò-Büchi (PB) reaction to discover the metabolic disturbance more precisely. Specifically, lipidomics revealed elevated levels of free fatty acids (FFA) alongside notable reductions in sphingomyelin (SM) and triacylglycerol (TAG) levels. Furthermore, the combination of PB reaction and molecular biology results indicated that short-term administration of emodin may lead to the accumulation of n-6 polyunsaturated fatty acids by up-regulating the expression of FASN, stearyl CoA desaturase 1 (SCD1), and cytosolic phospholipase A 2 (cPLA2). Simultaneously, up-regulation of cyclooxygenase-2 (Cox-2) expression was observed, potentially fostering the production of prostaglandin E2 (PGE2) and subsequent inflammation.

Effects of derivatization and probiotic transformation on the antioxidative activity of fruit polyphenols.

Fruits contain numerous polyphenols in the form of conjugates, which exhibit low antioxidant activity. Probiotic fermentation is a strategy to improve the antioxidant activity of these conjugated polyphenols by modifying their structure. However, the mechanisms underlying the effects of functional groups and derivatizations on the antioxidative activities of polyphenols and the antioxidation enhancement by probiotic biotransformation haven't been comprehensively explored. This review aimed to explore the structure-antioxidant activity relationships of four functional groups and three derivatizations in flavonoids and phenolic acids. Further, the review elucidated the antioxidant mechanisms underlying the biotransformation of flavonoids and phenolic acids as glycoside, methylated, and ester conjugates by probiotic biotransformation. Deglycosylation, demethylation, and hydrolysis catalyzed by enzymes produced by Bifidobacterium and Lactobacillus facilitated the conversion of conjugated polyphenols into flavonoids and phenolic acids with hydrolyzed forms and highly active functional groups, thereby increasing hydrogen supply and electron transfer capacity to enhance the antioxidant activity.

The prognostic implications of radiologic extranodal extension in the lymph nodes of patients with nasopharyngeal cancer.

Objective: This study was developed to explore the prognostic relevance of radiologic extranodal extension (rENE) in lymph node-positive nasopharyngeal carcinoma (NPC) patients. Materials and methods: A retrospective review of data from 249 eligible patients with NPC was performed, with magnetic resonance imaging scans being used for rENE grading. The prognostic value of rENE was assessed through univariate and multivariate analyses. Results: Log-rank tests revealed significant differences between patients with and without rENE in terms of overall survival, progression-free survival (PFS) and distant metastasis-free survival (DMFS). G2 and G3 patients tended to exhibit worse PFS and DMFS relative to G0/G1 patients (p < 0.05). Long-term chemotherapy cycles were associated with significant improvements in the PFS and DMFS of G2 and G3 patients. Conclusion: These results suggest that higher rENE grades (G2/G3) are independently associated with worse survival outcomes among NPC patients, with more aggressive treatment strategies potentially affording greater prognostic benefits to these individuals.

[Box: see text].

A robust bio-based polyurethane employed as surgical suture with help to promote skin wound healing.

Designing bio-based polyurethane materials with excellent mechanical, biocompatibility, and self-healing properties simultaneously is currently a significant challenge due to the increasing demands for high-performance materials. In this study, we propose an asymmetric backbone strategy utilizing bio-based polycarbonate as the soft segment, equimolar ratios of lysine diisocyanate and isophorone diisocyanate as asymmetric hard segments, and isophorone diamine as the chain extender. The resulting polyurethane elastomers exhibit excellent mechanical properties, including high tensile stress (46.1 MPa), toughness (213.9 MJ/m3), and fracture energy (98.47 kJ/m3). The polyurethane elastomers demonstrate good self-healing and recyclable properties under simple heat treatment. Furthermore, biological experiments confirm the degradability and bio-safety of the bio-based polyurethane elastomers, which have shown potential in accelerating wound healing in mice when used as surgical sutures. These findings highlight the promising prospects of the obtained polyurethane elastomers in various applications, including biomedicine, flexible sensing, and electronic components.

Gill lesions are the main cause of death in yellowfin seabream (Acanthopagrus latus) following infection with Amyloodinium ocellatum.

Amyloodiniosis, caused by the ectoparasite Amyloodinium ocellatum, affects the healthy development of mariculture. This study used a local infection method to identify the pathogenic target organ responsible for the death of infected fish. Comparing the relationship between the abundance of trophonts in gills and skin with the mortality of infected fish using local infection showed that severe gill infections cause the mortality of infected fish. At the 40 % survival rate of infected fish, the parasite abundance in the gill was 14,167 ± 4371. The gill filaments of the infected fish were structurally disordered, with pronounced lesions associated with the presence of trophonts, such as epithelial cell degeneration and massive lymphocytic infiltration. However, the skin showed no obvious pathological changes. The TUNEL assay showed a significant presence of apoptotic cells concentrated in the area of A. ocellatum infection. The trophonts on the gills developed faster than those parasitising the skin and fins. Microbiome analysis revealed that at the phylum level, Proteobacteria, Bacteroidota, and Firmicutes are abundant in the skin, while Verrucomicrobiota, Bacteroidota, and Proteobacteria are abundant in the gills of A. latus. Furthermore, A. ocellatum infection significantly reduced (p < 0.05) the richness and diversity of the gill microbial community of A. latus. Infection by A. ocellatum increased the relative abundance of several putative pathogenic bacteria (Flavobacterium and Nocardia) in the gill and skin of A. latus, possibly increasing the likelihood of disease in the host. In conclusion, these results evidenced that severe gill infections by A. ocellatum cause mortality in infected fish, which clarifies the direction for exploring the pathogenesis of amyloodiniosis.

InP/LiNbO3 Covalent Heterointerface Construction via an Asymmetric Plasma Activation Strategy for Hybrid Integrated Quantum Systems.

Lithium niobate (LiNbO3) is emerging as an appealing candidate for integrated optical applications with enhanced complexity, owing to its inherent abundant optoelectronic properties. To compensate for the inability of LiNbO3 to generate indistinguishable single photons, the evanescent coupling heterointerface constructed between III-V compound semiconductors (e.g., InP) and LiNbO3 through plasma activation provides a feasible solution for balancing the integration efficiency and interfacial stability while achieving sub-50 nm alignment accuracy between devices, thus offering ultracompact on-chip light sources for classical optoelectronics and quantum optics. However, a challenge remains in the formation of the InP/LiNbO3 platform due to the huge mismatch in the coefficient of thermal expansion. Here, we demonstrate the InP/LiNbO3 covalent heterointerface using an asymmetric plasma activation strategy. Different plasmas are used for the activation of InP and LiNbO3 specifically, balancing the enhancement of surface functional group density with the avoidance of defect generation effectively. More importantly, combined with surface comprehensive characterizations and interface performance, we determine that the introduction of ammonia solution enables the surface hydroxyl groups to be "effective" as LiNbO3 surface relaxation increases the chance of -OH groups' contact. Therefore, a robust covalent bond network is established across the InP/LiNbO3 interface at 80 °C with an enhanced bonding strength of 9.7 MPa. Moreover, a hybrid quantum photonic chip based on the InP/LiNbO3 platform is designed to compute the coupling efficiency and the impact of misalignment on it, demonstrating the potential of extending the platform to hybrid integrated quantum systems.