The Essential Oils Obtained from (Lonicerae japonicae Flos) Flower Buds Could Affect the Deposition of Sunflower Oil under Common High Temperature Conditions and the Traditional Frying Process in Maye.

The essential oil extracted from the flower buds of Lonicerae japonicae (LJEO) was employed in the high-temperature (65℃) accelerated preservation of sunflower oil. In the present investigation, the addition of the essential oil at a concentration of 800 ppm significantly inhibited the decrease in the oxidative stability of sunflower oil. This positive effect was achieved by significantly hindering the reduction in acidity value (AV), peroxide value (PV), ρ-anisidine value (AnV), the total oxidation value (TOTOX) (p < 0.01), and the levels of thiobarbituric acid reactive substance (TBARS), the absorbance at 232/268 nm (K232/K268) and total polar compounds (TPC) (p < 0.01). Besides, it also significantly enhances the sensory attributes of Maye, including taste, flavor, and appearance, improving its overall acceptability through the addition of certain potential fragrance molecules (p < 0.01). Furthermore, one of the primary chemical compounds in LJEO, eugenol, has demonstrated significant natural antioxidant properties in the traditional deep-frying procedure for the product, Maye. Consequently, together with eugenol, the essential oil LJEO could be employed as a possible effective antioxidant for the typical long-term preservation and even the traditional deep-frying procedures, and developed as effective antioxidant extracted from plants for the whole food industry.

Temporal variation in production performance, biochemical and oxidative stress markers, and gut microbiota in Pekin ducks during the late growth stage.

In the late growth stage of commercial Pekin ducks, a significant increase in feed intake and a decline in body weight gain have been observed, leading to impaired feed conversion efficiency. To address this issue, we investigated alterations in production performance, blood biochemical indices, ileum tissue architecture, and microbial community structure in Pekin ducks. The primary objective was to provide robust data supporting the improvement of meat duck production efficiency during the late growth stage (28-42-days-old). Forty 28-day-old Pekin ducks were randomly assigned to 8 replicates, with five ducks per replicate. The rearing period lasted 14 days, with feed and water provided ad libitum. Our findings indicated a significant increase in Pekin duck body and heart weights with advancing age (P < 0.05). Moreover, serum antioxidant enzyme and high-density lipoprotein concentrations significantly increased, whereas triglyceride levels decreased (P < 0.05). Notably, the height of the ileal villi was significantly reduced (P < 0.05). The microbial community structure of the ileum exhibited significant changes as ducks aged, accompanied by a substantial increase in microbial flora diversity, particularly with the formation of more tightly connected microbial network modules. Time-dependent enrichment was observed in microbial gene functions related to energy metabolism pathways. At the genus level, Sphingomonas and Subdoligranulum have emerged as crucial players in microbial differential functional pathways and network formation. These bacteria likely serve as the key driving factors in the dynamic microbial changes that occur in Pekin ducks over time. Overall, our findings suggest a potential decline in the absorption function of the small intestine and fat deposition performance of Pekin ducks during later growth stages, which may be attributed to the maturation and proliferation of the gut microbial community.

Repurposing Anticancer Drugs Targeting the MAPK/ERK Signaling Pathway for the Treatment of Respiratory Virus Infections.

Respiratory virus infections remain a significant challenge to human health and the social economy. The symptoms range from mild rhinitis and nasal congestion to severe lower respiratory tract dysfunction and even mortality. The efficacy of therapeutic drugs targeting respiratory viruses varies, depending upon infection time and the drug resistance engendered by a high frequency of viral genome mutations, necessitating the development of new strategies. The MAPK/ERK pathway that was well delineated in the 1980s represents a classical signaling cascade, essential for cell proliferation, survival, and differentiation. Since this pathway is constitutively activated in many cancers by oncogenes, several drugs inhibiting Raf/MEK/ERK have been developed and currently used in anticancer treatment. Two decades ago, it was reported that viruses such as HIV and influenza viruses could exploit the host cellular MAPK/ERK pathway for their replication. Thus, it would be feasible to repurpose this category of the pathway inhibitors for the treatment of respiratory viral infections. The advantage is that the host genes are not easy to mutate such that the drug resistance rarely occurs during short-period treatment of viruses. Therefore, in this review we will summarize the research progress on the role of the MAPK/ERK pathway in respiratory virus amplification and discuss the potential of the pathway inhibitors (MEK inhibitors) in the treatment of respiratory viral infections.

Construction of luminescent dye@MOF platforms for sensing antibiotics with enhanced selectivity and sensitivity.

The fabrication of luminescent dye@MOF composites has received extensive attentions in the development of realistic sensing applications. Herein, based on two anionic In-MOFs with different pore structure (1 and 2), the charge and size dependent ion-exchange of cationic dyes was investigated, and consequently four luminescent dye@MOF composites (DMASM@1/2 and RhB@1/2) were successfully fabricated and importantly can be regarded as ideal platforms for better understanding of the factors affecting the construction of dye@MOF composites, which may closely related to a well match between the intrinsic properties and size/charge of the fluorescent molecules and the porosity, structure character of the MOF hosts. Furthermore, these four dye@MOF composites were utilized for sensing of different kinds of antibiotics, demonstrating enhanced selectivity and sensitivity. DMASM@1/2 demonstrated excellent selectivity and sensitivity for NFT and NFZ antibiotics, while RhB@1/2 exhibited excellent selectivity and sensitivity for MDZ and DTZ antibiotics. Systematic analysis of the detection mechanism revealed that different energy transfer efficiency and interaction between MOF frameworks and different types of guest dyes led to different selectivity and detection mechanisms for antibiotics. Moreover, high selectivity and sensitivity, low LOD and extraordinary recycling capacity of four dye@MOF composites in the detection of antibiotics promote their excellent prospect in the further practical application.

The regulatory role of m6A modification in the maintenance and differentiation of embryonic stem cells.

As the most prevalent and reversible internal epigenetic modification in eukaryotic mRNAs, N 6-methyladenosine (m6A) post-transcriptionally regulates the processing and metabolism of mRNAs involved in diverse biological processes. m6A modification is regulated by m6A writers, erasers, and readers. Emerging evidence suggests that m6A modification plays essential roles in modulating the cell-fate transition of embryonic stem cells. Mechanistic investigation of embryonic stem cell maintenance and differentiation is critical for understanding early embryonic development, which is also the premise for the application of embryonic stem cells in regenerative medicine. This review highlights the current knowledge of m6A modification and its essential regulatory contribution to the cell fate transition of mouse and human embryonic stem cells.

Structure-Mechanics Principles and Mechanobiology of Fibrocartilage Pericellular Matrix: A Pivotal Role of Type V Collagen.

The pericellular matrix (PCM) is the immediate microniche surrounding resident cells in various tissue types, regulating matrix turnover, cell-matrix cross-talk and disease initiation. This study elucidated the structure-mechanical properties and mechanobiological functions of the PCM in fibrocartilage, a family of connective tissues that sustain complex tensile and compressive loads in vivo. Studying the murine meniscus as the model tissue, we showed that fibrocartilage PCM contains thinner, random collagen fibrillar networks that entrap proteoglycans, a structure distinct from the densely packed, highly aligned collagen fibers in the bulk extracellular matrix (ECM). In comparison to the ECM, the PCM has a lower modulus and greater isotropy, but similar relative viscoelastic properties. In Col5a1 +/- menisci, the reduction of collagen V, a minor collagen localized in the PCM, resulted in aberrant fibril thickening with increased heterogeneity. Consequently, the PCM exhibited a reduced modulus, loss of isotropy and faster viscoelastic relaxation. This disrupted PCM contributes to perturbed mechanotransduction of resident meniscal cells, as illustrated by reduced intracellular calcium signaling, as well as upregulated biosynthesis of lysyl oxidase and tenascin C. When cultured in vitro, Col5a1 +/- meniscal cells synthesized a weakened nascent PCM, which had inferior properties towards protecting resident cells against applied tensile stretch. These findings underscore the PCM as a distinctive microstructure that governs fibrocartilage mechanobiology, and highlight the pivotal role of collagen V in PCM function. Targeting the PCM or its molecular constituents holds promise for enhancing not only meniscus regeneration and osteoarthritis intervention, but also addressing diseases across various fibrocartilaginous tissues.

YAP inhibits NF-κB signaling and ccRCC growth by opposing p65-ZHX2 cooperativity.

Hippo pathway functions as a tumor suppressor pathway by inhibiting the oncogenic potential of pathway effectors YAP/TAZ. However, YAP can also function as a context-dependent tumor suppressor in several types of cancer including clear cell renal cell carcinomas (ccRCC). Here we show that YAP blocks NF-κB signaling in ccRCC to inhibit cancer cell growth. Mechanistically, YAP inhibits the expression of ZHX2, a critical p65 co-factor in ccRCC. Furthermore, YAP competes with ZHX2 for binding to p65. Consequently, elevated nuclear YAP blocks the cooperativity between ZHX2 and p65, leading to diminished NF-κB target gene expression. Pharmacological inhibition of Hippo/MST1/2 blocked NF-κB transcriptional program and suppressed ccRCC cancer cell growth, which can be rescued by ZHX2/p65 overexpression. Our study uncovers a novel crosstalk between the Hippo and NF-κB pathways and its involvement in ccRCC growth inhibition, suggesting that targeting the Hippo pathway may provide a therapeutical opportunity for ccRCC treatment.

Integrated Acetabular Prosthesis Versus Bone Grafting in Total Hip Arthroplasty for Crowe Type II and III Hip Dysplasia: A Retrospective Case-Control Study.

OBJECTIVE: Many methods of acetabular reconstruction with total hip arthroplasty (THA) for Crowe type II and III adult developmental dysplasia of the hip (DDH) acetabular bone defect have been implemented clinically. However, there was no study comparing the results of integrated acetabular prosthesis (IAP) with bone grafting (BG). This study aims to investigate the efficacy of IAP and BG for acetabular reconstruction in Crowe type II and III DDH. METHODS: The clinical data of 45 patients with unilateral Crowe type II and III DDH who underwent THA from January 2020 to January 2023 were retrospectively analyzed. The patients were divided into two groups: 25 patients using 3D-printed IAP (IAP group) and 20 patients using BG (BG group). The operation time and intraoperative blood loss were recorded. The clinical outcomes were assessed by Harris Hip Score (HHS) and full weight-bearing time. The radiological outcomes were evaluated by the radiological examination. Accordingly, intraoperative and postoperative complications were observed as well. The data between the two groups were compared by independent sample t-tests and the Mann-Whitney U rank sum test. RESULTS: There were no significant differences between the two groups in Harris Hip Score (HHS) (preoperative, 6 months postoperative, and the last follow-up), leg length discrepancy (LLD), cup inclination, cup anteversion, vertical center of rotation (V-COR), horizontal center of rotation (H-COR) (p > 0.05). The mean HHS in the IAP group was higher than in the BG group at 1 and 3 months postoperative (p < 0.001). The mean surgical time and blood loss in the IAP group were less than in the BG group (p < 0.001). The mean full weight-bearing time in the IAP group was shorter than in the BG group (p < 0.01). No complications were observed in either group during the follow-up period. CONCLUSION: IAP and BG have similar radiographic outcomes and long-term clinical efficacy in THA for Crowe type II and III DDH, but the IAP technique has higher surgical safety and facilitates the recovery of hip joint function, which is worthy of clinical promotion.

[Simultaneous determination of maltol and seventeen saponins in red and black ginseng by UPLC-PDA wavelength switching method].

This study developed a UPLC-PDA wavelength switching method to simultaneously determine the content of maltol and seventeen saponins in red and black ginseng and compared the quality differences of two different processed products of red and black ginseng. A Waters HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) at 30 ℃ was adopted, with the mobile phase of acetonitrile(A) and water containing 0. 1% phosphoric acid(B) under gradient elution, the flow rate of 0. 3 m L·min~(-1), and the injection volume of 2 µL.The wavelength switching was set at 273 nm within 0-11 min and 203 nm within 11-60 min. The content results of multiple batches of red and black ginseng samples were analyzed by the hierarchical cluster analysis(HCA) and principal component analysis(PCA) to evaluate the quality difference. The results showed that the 18 constituents exhibited good linear relationships within certain concentration ranges, with the correlation coefficients(r) greater than 0. 999 1. The relative standard deviations(RSDs) of precision,repeatability, and stability were all less than 5. 0%. The average recoveries ranged from 95. 93% to 104. 2%, with an RSD of 1. 8%-4. 2%. The content determination results showed that the quality of red and black ginseng samples was different, and the two types of processed products were intuitively distinguished by HCA and PCA. The method is accurate, reliable, and reproducible. It can be used to determine the content of maltol and seventeen saponins in red and black ginseng and provide basic information for the quality evaluation and comprehensive utilization of red and black ginseng.

Effect of metformin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from real-world studies.

PURPOSE: Metformin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between metformin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of metformin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of metformin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed. RESULTS: The across studies results show that metformin use associated with lower incidence of PCa (RR: 0.82, 95% CI: 0.74-0.91). Metformin use was also found to reduce PCa recurrence, but the results were not statistically significant (RR: 0.97, 95% CI: 0.81-1.15). Metformin use was not associated with PCa mortality (RR: 0.94, 95% CI: 0.81-1.09). The results of subgroup analyses indicated that the type of study was a cohort study and the population came from both Asia and Europe showed that taking metformin reduced the incidence of PCa. A linear correlation was found between the duration of metformin use and its protective effect. CONCLUSIONS: This meta-analysis revealed an independent correlation between metformin use and reduced incidence of PCa. Metformin use was not associated with either PCa recurrence rate or mortality. Furthermore, the effect of metformin on PCa incidence was found to be related to duration.

YTH domain family protein 3 accelerates non-small cell lung cancer immune evasion through targeting CD8+ T lymphocytes.

Immune evasion is one of the critical hallmarks of malignant tumors, especially non-small cell lung cancer (NSCLC). Emerging findings have illustrated the roles of N6-methyladenosine (m6A) on NSCLC immune evasion. Here, this study investigated the function and underlying mechanism of m6A reader YTH domain family protein 3 (YTHDF3) on NSCLC immune evasion. YTHDF3 was found to be highly expressed in NSCLC tissue and act as an independent prognostic factor for overall survival. Functionally, up-regulation of YTHDF3 impaired the CD8+ T antitumor activity to deteriorate NSCLC immune evasion, while YTHDF3 silencing recovered the CD8+ T antitumor activity to inhibit immune evasion. Besides, YTHDF3 up-regulation reduced the apoptosis of NSCLC cells. Mechanistically, PD-L1 acted as the downstream target for YTHDF3, and YTHDF3 could upregulate the transcription stability of PD-L1 mRNA. Overall, YTHDF3 targeted PD-L1 to promote NSCLC immune evasion partially through escaping effector cell cytotoxicity CD8+ T mediated killing and antitumor immunity. In summary, this study provides an essential insight for m6A modification on CD8+ T cell-mediated antitumor immunity in NSCLC, which might inspire an innovation for lung cancer tumor immunotherapy.

A phosphatase-like nanomaterial promotes autophagy and reprograms macrophages for cancer immunotherapy.

Macrophages are plastic and play a key role in the maintenance of tissue homeostasis. In cancer progression, macrophages also take part in all processes, from initiation to progression, to final tumor metastasis. Although energy deprivation and autophagy are widely used for cancer therapy, most of these strategies do not target macrophages, resulting in undesired effects and unsatisfactory outcomes for cancer immunotherapy. Herein, we developed a lanthanum nickel oxide (LNO) nanozyme with phosphatase-like activity for ATP hydrolysis. Meanwhile, the autophagy of macrophages induced by LNO promotes the polarization of macrophages from M2-like macrophages (M2) to M1-like macrophages (M1) and reduces tumor-associated macrophages in tumor-bearing mice, exhibiting the capability of killing tumor-associated macrophages and antitumor effects in vivo. Furthermore, pre-coating the surface of LNO with a myeloid cell membrane significantly enhanced antitumor immunity. Our findings demonstrate that phosphatase-like nanozyme LNO can specifically induce macrophage autophagy, which improves therapeutic efficacy and offers valuable strategies for cancer immunotherapy.

Polysaccharides extracted from common buckwheat (Fagopyrum esculentum) attenuate cognitive impairment via suppressing RAGE/p38/NF-κB signaling and dysbiosis in AlCl3-treated rats.

Patients may find it challenging to accept several FDA-approved drugs for Alzheimer's disease (AD) treatment due to their unaffordable prices and side effects. Despite the known antioxidant, anti-inflammatory, and microbiota-regulating effects of common buckwheat (Fagopyrum esculentum) polysaccharides (FEP), their specific role in preventing AD has not been determined. Here, this study investigated the preventive effects of FEP on AD development in AlCl3-treated rats. The physical properties of FEP were evaluated using X-ray diffraction, FTIR, TGA, DSC, monosaccharide composition, molecular weight, and scanning electron microscopy. The results demonstrated that FEP administration improved memory and learning ability in AlCl3-treated rats. Additionally, AD pathological biomarkers (APP, BACE1, Aß1-42, and p-TauSer404), inflammatory-associated proteins (IL-1ß, IL-6, TNF-α, and Iba1), and MDA and the RAGE/p38/NF-κB pathway were elevated in AlCl3-treated rats. Moreover, these effects were reversed by the upregulation of LRP1, anti-inflammatory cytokines (IL-4 and IL-10), antioxidant enzymes (SOD and catalase), and autophagy proteins (Atg5, Beclin-1, and LC3B). Furthermore, FEP treatment increased the levels of short-chain fatty acids (SCFAs) and the abundance of SCFAs-producing microbes ([Eubacterium]_xylanophilum_group, Lachnospiraceae_NK4A136_group, Lactobacillus). Overall, FEP mitigated oxidative stress, RAGE/p38/NF-κB-mediated neuroinflammation, and AD-associated proteins by upregulating autophagy and SCFA levels, which led to the amelioration of cognitive impairment through microbiota-gut-brain communication in AlCl3-treated rats.

Association of sudden sensorineural hearing loss with meteorological factors: a time series study in Hefei, China, and a literature review.

Air pollution can cause disease and has become a major global environmental problem. It is currently believed that air pollution may be related to the progression of SSNHL. As a rapidly developing city in recent years, Hefei has serious air pollution. In order to explore the correlation between meteorological variables and SSNHL admissions, we conducted this study. This study investigated the short-term associations between SSNHL patients admitted to the hospital and Hefei climatic variables. The daily data on SSNHL-related hospital admissions and meteorological variables containing mean temperature (T-mean; °C), diurnal temperature range (DTR; °C), atmospheric pressure (AP; Hp), and relative humidity (RH; %), from 2014 to 2021 (2558 days), were collected. A time-series analysis integrating distributed lag non-linear models and generalized linear models was used. PubMed, Embase, Cochrane Library, and Web of Science databases were searched. Literature published up to August 2023 was reviewed to explore the potential impact mechanisms of meteorological factors on SSNHL. The mechanisms were determined in detail, focusing on wind speed, air pressure, temperature, humidity, and air pollutants. Using a median of 50.00% as a baseline, the effect of exceedingly low T-mean in the single-day hysteresis effect model began at a lag of 8 days (RR = 1.032, 95% CI: 1.001 ~ 1.064). High DTR affected the admission rate for SSNHL on lag 0 day. The significance of the effect was the greatest on that day (RR = 1.054, 95% CI: 1.007 ~ 1.104) and then gradually decreased. High and exceedingly high RH affected the admission rate SSNHL on lag 0 day, and these effects lasted for 8 and 7 days, respectively. There were significant associations between all grades of AP and SSNHL. This is the first study to assess the effect of meteorological variables on SSNHL-related admissions in China using a time-series approach. Long-term exposures to high DTR, RH values, low T-mean values, and all AP grades enhance the incidence of SSNHL in residents. Limiting exposure to extremes of ambient temperature and humidity may reduce the number of SSNHL-related hospital visits in the region. It is advisable to maintain a suitable living environment temperature and avoid extreme temperature fluctuations and high humidity. During periods of high air pollution, it is recommended to stay indoors and refrain from outdoor exercise.

Cold atmospheric plasma can effectively disinfect SARS-CoV-2 in the wastewater.

COVID-19 is currently pandemic and the detection of SARS-CoV-2 variants in wastewater is causing widespread concern. Herein, cold atmospheric plasma (CAP) is proposed as a novel wastewater disinfection technology that effectively inactivates SARS-CoV-2 transcription- and replication-competent virus-like particles, coronavirus GX_P2V, pseudotyped SARS-CoV-2 variants, and porcine epidemic diarrhoea virus in a large volume of water within 180 s (inhibition rate > 99%). Further, CAP disinfection did not adversely affect the viability of various human cell lines. It is identified that CAP produced peroxynitrite (ONOO-), ozone (O3), superoxide anion radicals (O2 -), and hydrogen peroxide (H2O2) as the major active substances for coronavirus disinfection. Investigation of the mechanism showed that active substances not only reacted with the coronavirus spike protein and affected its infectivity, but also destroyed the nucleocapsid protein and genome, thus affecting virus replication. This method provides an efficient and environmentally friendly strategy for the elimination of SARS-CoV-2 and other coronaviruses from wastewater.

Activating transcription factor 6 contributes to cisplatin­induced ototoxicity via regulating the unfolded proteins response.

As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.

Three-Pillar Expansive Craniotomy in Children with Acute Ruptured Supratentorial Brain Arteriovenous Malformations.

OBJECTIVE: Acute rupture and hemorrhage of pediatric brain arteriovenous malformations (AVMs) may lead to cerebral herniation or intractable intracranial hypertension, necessitating emerging surgical interventions to alleviate intracranial pressure. However, there is still controversy regarding the timing of treatment for ruptured AVMs. This study aimed to assess the feasibility of utilizing three-pillar expansive craniotomy (3PEC) at different times during the treatment of pediatric ruptured supratentorial AVMs. METHODS: A retrospective analysis was conducted on all consecutive cases of acute rupture in supratentorial AVM children who underwent 3PEC at a single institution from 2020 to 2022. General information, clinical characteristics, radiological data, and prognosis were reviewed and analyzed. RESULTS: Thirteen children were included in the analysis. The intracranial pressure of all patients decreased to below 15 mmHg within 10 days. The expansion volume of the cranial cavity of the patients increased by 18.3 cm3 (95% confidence interval, 10.2-26.3; P < 0.001) compared to the hematoma volume. None of the patients required decompressive craniectomy due to intractable intracranial hypertension caused by cerebral swelling. The median waiting period for patients with delayed AVMs treatment was 8 days, during which no rebleeding occurred. CONCLUSIONS: Emergency intervention with 3PEC in children experiencing acutely ruptured supratentorial AVMs appears to be feasible. For children requiring delayed management of the AVMs, 3PEC may diminish the risk of rebleeding during the waiting period and shorten the waiting period.

nnSegNeXt: A 3D Convolutional Network for Brain Tissue Segmentation Based on Quality Evaluation.

Accurate and automated segmentation of brain tissue images can significantly streamline clinical diagnosis and analysis. Manual delineation needs improvement due to its laborious and repetitive nature, while automated techniques encounter challenges stemming from disparities in magnetic resonance imaging (MRI) acquisition equipment and accurate labeling. Existing software packages, such as FSL and FreeSurfer, do not fully replace ground truth segmentation, highlighting the need for an efficient segmentation tool. To better capture the essence of cerebral tissue, we introduce nnSegNeXt, an innovative segmentation architecture built upon the foundations of quality assessment. This pioneering framework effectively addresses the challenges posed by missing and inaccurate annotations. To enhance the model's discriminative capacity, we integrate a 3D convolutional attention mechanism instead of conventional convolutional blocks, enabling simultaneous encoding of contextual information through the incorporation of multiscale convolutional features. Our methodology was evaluated on four multi-site T1-weighted MRI datasets from diverse sources, magnetic field strengths, scanning parameters, temporal instances, and neuropsychiatric conditions. Empirical evaluations on the HCP, SALD, and IXI datasets reveal that nnSegNeXt surpasses the esteemed nnUNet, achieving Dice coefficients of 0.992, 0.987, and 0.989, respectively, and demonstrating superior generalizability across four distinct projects with Dice coefficients ranging from 0.967 to 0.983. Additionally, extensive ablation studies have been implemented to corroborate the effectiveness of the proposed model. These findings represent a notable advancement in brain tissue analysis, suggesting that nnSegNeXt holds the promise to significantly refine clinical workflows.

Synthetic genomic nanomedicine with triple-responsiveness for systemic anti-tumor therapy.

To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core-shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.