An iron-containing nanomedicine for inducing deep tumor penetration and synergistic ferroptosis in enhanced pancreatic cancer therapy.

Pancreatic cancer is an aggressive and challenging malignancy with limited treatment options, largely attributed to the dense tumor stroma and intrinsic drug resistance. Here, we introduce a novel iron-containing nanoparticle formulation termed PTFE, loaded with the ferroptosis inducer Erastin, to overcome these obstacles and enhance pancreatic cancer therapy. The PTFE nanoparticles were prepared through a one-step assembly process, consisting of an Erastin-loaded PLGA core stabilized by a MOF shell formed by coordination between Fe3+ and tannic acid. PTFE demonstrated a unique capability to repolarize tumor-associated macrophages (TAMs) into the M1 phenotype, leading to the regulation of dense tumor stroma by modulating the activation of tumor-associated fibroblasts (TAFs) and reducing collagen deposition. This resulted in enhanced nanoparticle accumulation and deep penetration, as confirmed by in vitro multicellular tumor spheroids and in vivo mesenchymal-rich subcutaneous pancreatic tumor models. Moreover, PTFE effectively combated tumor resistance by synergistically employing the Fe3+-induced Fenton reaction and Erastin-induced ferroptosis, thereby disrupting the redox balance. As a result, significant tumor growth inhibition was achieved in mice-bearing tumor model. Comprehensive safety evaluations demonstrated PTFE's favorable biocompatibility, highlighting its potential as a promising therapeutic platform to effectively address the formidable challenges in pancreatic cancer treatment.

Non-small cell lung cancer and metabolism research from 2013 to 2023: a visual analysis and bibliometric study.

Background: As one of the most prevalent primary lung tumors, non-small cell lung cancer (NSCLC) has garnered considerable research interest due to its high metastasis rates and poor prognosis outcomes. Across different cancer types, metabolic processes are required for tumors progression and growth, thus interfering with such processes in NSCLC may therapeutically viable for limiting/halting disease progression. Therefore, comprehending how metabolic processes contribute to growth and survival mechanisms in cancers, including NSCLC, may elucidate key functions underpinning tumor cell metabolism. However, no bibliometric analyses have been published in this field, therefore we address this knowledge gap here. Methods: Between 2013 and 2023 (December 28th), articles related to the NSCLC and metabolism (NSCLC-Met) field were retrieved from the Web of Science Core Collection (WoSCC). To fully dissect NSCLC-Met research directions and articles, we used the Bibliometrix package in R, VOSviewer and CiteSpace software to visually represent global trends and hotspots. Results: Between 2013 and 2023, 2,246 NSCLC-Met articles were retrieved, with a continuous upward trend and rapid development observed year on year. Cancers published the most articles, with Cancer Research recording the highest average citation numbers. Zhang Li from China was the most prolific author, but the highest number of authors came from the USA. China, USA, and Italy were the top three countries with the highest number of published articles, with close cooperation identified between countries. Recent hotspots and research directions were reflected by "lung adenocarcinoma", "immunotherapy", "nivolumab", "checkpoint inhibitors", "blockade", and "pembrolizumab", while "gut microbiome", "egfr" and "dose painting" were important topics for researchers. Conclusion: From our analyses, scientists can now explore new hotspots and research directions in the NSCLC-Met field. Further in-depth research in this field will undoubtedly provide more new insights on disease diagnostics, treatment, and prognostics.

[Analysis of 141 cases with benign upper airway occupying in infant].

Objective:To analyze and summarize the clinical characteristics, diagnosis, treatment and prognosis of benign upper airway space occupancy in infants. Methods:The clinical data of 141 cases with begin upper airway space from January 2012 to January 2022 were analyzed. Among them, 101 were male and 68 were female, the age is 0-3 years old. In which there were 24 newborns. The clinical characteristics, auxiliary examination and treatment results were summarized and analyzed. Results:The main clinical manifestations of 141 infants were dyspnea and/or laryngeal wheezing, including 116 cases of congenital cyst of tongue, 15 cases of hair polyps, 4 cases of nasopharyngeal second pharyngeal fissure cysts, 2 cases of congenital laryngeal cysts, 2 cases of pharyngeal bronchial cyst, 1 case of nasopharyngeal teratoma and 1 case of myofibroma. All the infants had completed the corresponding examination and treatment. The diagnosis was clear, and there was no missed diagnosis or misdiagnosis. Among them, 19 infants with congenital cyst of tongue were given cyst puncture to relieve dyspnea. 2 cases of congenital cyst of tongue recurred half a year after operaion, and then they underwent reoperation. The prognosis of the remaining infants were good. Conclusion:The most common occupying of benign upper airway space occupancy is cyst, and low-temperature plasma resection under endoscope is the main treatment method. Timely puncture therapy is also a safe and effective treatment for infants who are dyspnea and life threatening.

Electroacupuncture suppresses neuronal ferroptosis to relieve chronic neuropathic pain.

Growing evidence supports the analgesic efficacy of electroacupuncture (EA) in managing chronic neuropathic pain (NP) in both patients and NP models induced by peripheral nerve injury. However, the underlying mechanisms remain incompletely understood. Ferroptosis, a novel form of programmed cell death, has been found to be activated during NP development, while EA has shown potential in promoting neurological recovery following acute cerebral injury by targeting ferroptosis. In this study, to investigate the detailed mechanism underlying EA intervention on NP, male Sprague-Dawley rats with chronic constriction injury (CCI)-induced NP model received EA treatment at acupoints ST36 and GV20 for 14 days. Results demonstrated that EA effectively attenuated CCI-induced pain hypersensitivity and mitigated neuron damage and loss in the spinal cord of NP rats. Moreover, EA reversed the oxidative stress-mediated spinal ferroptosis phenotype by upregulating reduced expression of xCT, glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH1) and superoxide dismutase (SOD) levels, and downregulating increased expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), malondialdehyde levels and iron overload. Furthermore, EA increased the immunofluorescence co-staining of GPX4 in neurons cells of the spinal cord of CCI rats. Mechanistic analysis unveiled that the inhibition of antioxidant pathway of Nrf2 signalling via its specific inhibitor, ML385, significantly countered EA's protective effect against neuronal ferroptosis in NP rats while marginally diminishing its analgesic effect. These findings suggest that EA treatment at acupoints ST36 and GV20 may protect against NP by inhibiting neuronal ferroptosis in the spinal cord, partially through the activation of Nrf2 signalling.

Spatiotemporal heterogeneity of inundation pattern of floodplain lake wetlands and impact on wetland vegetation.

The inundation pattern is an important ecohydrological indicator for studying floodplain lake wetlands, as it is the key factor affecting the wetland vegetation distribution patterns. Poyang Lake, the largest freshwater lake in China, is a typical floodplain lake wetland. This study presents a hydrodynamic model and vegetation survey of Poyang Lake, analyzed the spatiotemporal heterogeneity of the inundation pattern (inundation duration and depth), assessed the response patterns of wetland vegetation concerning the inundation pattern, and examined the impact of the proposed Poyang Lake Water Conservancy Hub (PLWCH) on the inundation pattern and wetland vegetation. The results revealed that the inundation pattern of Poyang Lake had significant spatial heterogeneity. Inundation pattern was found to have a significant impact on the vegetation succession. The response relationship between the distribution areas of different wetland vegetation types and inundation pattern was in accordance with the Gaussian curve, and the ecological threshold range of the Carex spp. community was the greatest. Owing to factors such as climate change and anthropogenic activities, the inundation pattern of Poyang Lake varied significantly since 2003, with the average inundation duration and average inundation depth decreasing by 15 d and 0.32 m, respectively. Consequently, the spatial distribution of wetland vegetation changed significantly, whereby the Carex spp., Polygonum criopolitanum, and Phalaris arundinacea communities extended down to the lower elevation zone. In the future, the PLWCH may result in increases in the inundation duration and depth, restrain the downward vegetation extension trend, and promote the vegetation to move to higher elevations similar to the status prior to 2003. These findings provide a detailed description of the spatiotemporal heterogeneity of the inundation pattern and the drivers of wetland vegetation distribution patterns in floodplain lake wetlands, serving as a scientific basis for conservation and restoration of these ecosystems.

Mn-based cGAS-STING activation for tumor therapy.

Immunotherapy has efficiently revolutionized the treatment of human neoplastic diseases. However, the overall responsive rate of current immunotherapy is still unsatisfactory, benefiting only a small proportion of patients. Therefore, significant attention has been paid to the modulation of tumor microenvironment (TME) for the enhancement of immunotherapy. Interestingly, recent studies have shown that cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) was initially found as an innate immune sensor to recognize cytoplasmic DNA (such as bacterial, viral, micronuclei, and mitochondrial). It is a promising signaling pathway to activate antitumor immune responses via type I interferon production. Notably, Mn2+ was found to be a critical molecule to sensitize the activation of the cGAS-STING pathway for better immunotherapy. This activation led to the development of Mn2+-based strategies for tumor immunotherapy via the activation of the cGAS-STING pathway. In this critical review, we aimed to summarize the recent progress of this field, focusing on the following three aspects. First, we briefly introduced the signaling pathway of cGAS-STING activation, and its regulation effect on the antitumor immunity cycle has been discussed. Along with this, several agonists of the cGAS-STING pathway were introduced with their potential as immunotherapeutic drugs. Then, the basic biological functions of Mn2+ have been illustrated, focusing on its critical roles in the cGAS-STING pathway activation. Next, we systematically reviewed the Mn2+-based strategies for tumor immunotherapy, which can be classified by the methods based on Mn2+ alone or Mn2+ combined with other therapeutic modalities. We finally speculated the future perspectives of the field and provided rational suggestions to develop better Mn2+-based therapeutics.

Derivation of new resistance principle on flow-induced morphological response of flexible vegetation.

Water flow under vegetated environments is a noteworthy research topic in environmental hydraulics and restoration ecology, and this research is particularly important for maintaining water transport and streambed stability in water ecosystems. The calculation of the resistance coefficient in vegetated water flow is the core of this research. But there are still problems such as complex expressions and low simulation accuracy in this research field. To solve this scientific problem, this research, based on the theoretical study of environmental hydraulics and genetic algorithm, selected three basic parameters of vegetation submergence, resistance length and curvature degree, and successfully constructed the formula for calculating the resistance coefficient for flexible vegetated flow by using a wide range of data sets. New quantitative relationship between the drag coefficient and the relative roughness of flexible vegetation was established in this study. The formula of drag coefficients for flexible vegetation conditions has a more concise form and can be successfully applied to both flexible and rigid vegetation. As flexible vegetation is deformed under the action of water flow, and the quantitative expressions of Vogel number and relative roughness are given quantitatively through the analysis of its physical properties. Overall, this study improves the basic theoretical study of vegetated flow in environmental fluid dynamics and provides scientific theoretical support for vegetation restoration.

Risk factors and antibiotic sensitivity of aerobic bacteria in Chinese children with adenoid hypertrophy.

BACKGROUND: Bacterial infection of adenoid is currently considered to be an important cause of adenoid hypertrophy (AH) in children. Although several bacteriology studies on adenoid diseases have been reported, the aerobic bacterial study regarding risk factors and antibiotic sensitivity of AH in Chinese children is lacking. This study aims to investigate the risk factors for aerobic bacterial colonization of AH in Chinese children and to elucidate aerobic bacterial profiles and antibiotic sensitivity. METHODS: Samples were collected from the adenoid core and surface tissue of 466 children undergoing adenoidectomy. Aerobic cultures and antibiotic sensitivity were observed. The risk factors for bacterial colonization of adenoid were analyzed statistically. RESULTS: A total of 143 children could be detected opportunistic pathogens in adenoid surface and/or core tissue, with a carriage rate of 30.7%. The presence of chronic rhinosinusitis, tonsillar hypertrophy and adenoidal size were the risk factors for aerobic bacterial colonization of adenoid in univariate analysis. Multivariate analysis showed that chronic rhinosinusitis and tonsil hypertrophy were significant variables associated with the aerobic bacterial colonization. The most frequently isolated aerobic bacteria were Haemophilus influenzae, followed by Staphylococcus aureus and Streptococcus pneumoniae. There was no statistically significant difference in bacterial species between the adenoid surface and core. The above common bacteria were more sensitive to cephalosporins and quinolones antibiotics, and significantly resistant to penicillin antibiotics and non-ß-lactamase inhibitors. CONCLUSION: Our results provide recent aerobic bacterial profiles for AH among Chinese children and confirm the risk factors and antibiotic sensitivity. This study contributes to understanding the role of different risk factors in the development of AH and will be helpful to the treatment of AH among Chinese children.

[Cholesteatoma of the middle ear combined with intracranial and extracranial complications in children: a case report].

In this paper, a case of middle ear cholesteatoma with sigmoid sinus thrombophlebitis and retroauricular subperiosteal abscess was reported. The female patient was hospitalized with bilateral ear abscess for more than 20 days and fever with vomiting for 14 days. Anti-infection treatment after admission, emergency right mastoid radical resection and tympanoplasty were performed under general anesthesia. The patient recovered well after surgery, and there was no recurrence after in the follow-up for more than 2 years.The clinical manifestations, imaging features and prognosis of this disease were discussed and analyzed in the paper.

Patterns and drivers of the belowground bud bank in alpine grasslands on the Qinghai-Tibet Plateau.

Introduction: In grassland ecosystems dominated by asexual plants, the maintenance, renewal, and resistance of plant populations to disturbance are more dependent on the belowground bud bank (BBB). However, the response of the BBB to environmental factors in the alpine grassland of the Qinghai-Tibet Plateau (QTP) is still unknown. Methods: Therefore, a transect survey was conducted to measure the size and scale of BBB and 21 factors in the alpine grassland of the QTP. In addition, the critical driving factors of BBB were screened by boost regression tree analysis, and a structural equation model (SEM) was employed to express the path coefficients of the key factors on the BBB size. Results: The results showed that BBB size had no significant geographical pattern in the QTP, and the BBB size was mainly accounted for by soil leucine aminopeptidase (LAP, 17.32%), followed by Margalef and Shannon -Wiener indices of plants (12.63% and 9.24%, respectively), and precipitation (9.23%). SEM further indicated significant positive effects of plant diversity (scored at 0.296) and precipitation (scored at 0.180) on BBB size, and a significant negative effect of LAP (scored at 0.280) on BBB size. Discussion: Generally, the findings allow for better understanding of the regulated mechanisms of BBB size and the importance of the role of bud bank in the restoration of the grassland ecosystem.

Embedding Regularizer Learning for Multi-View Semi-Supervised Classification.

Classification remains challenging when confronted with the existence of multi-view data with limited labels. In this paper, we propose an embedding regularizer learning scheme for multi-view semi-supervised classification (ERL-MVSC). The proposed framework integrates diversity, sparsity and consensus to dexterously manipulate multi-view data with limited labels. To encourage diversity, ERL-MVSC recasts a linear regression model to derive view-specific embedding regularizers and automatically determines their weights. This is able to tactfully incorporate complementary information of different views. To ensure sparsity, ERL-MVSC imposes l2,1 -norm on a fused embedding regularizer to exploit the sparse local structure of samples, thereby conveying valuable classification information and enhancing the robustness against noise/outliers. To enhance consensus, ERL-MVSC learns a shared predicted label matrix, which serves as the comment target of multi-view classification. With these techniques, we formulate ERL-MVSC as a joint optimization problem of an embedding regularizer and a predicted label matrix, which can be solved by a coordinate descent method. Extensive experimental results on real-world datasets demonstrate the effectiveness and superiority of the proposed algorithm.

Joint Learning of Latent Similarity and Local Embedding for Multi-View Clustering.

Spectral clustering has been an attractive topic in the field of computer vision due to the extensive growth of applications, such as image segmentation, clustering and representation. In this problem, the construction of the similarity matrix is a vital element affecting clustering performance. In this paper, we propose a multi-view joint learning (MVJL) framework to achieve both a reliable similarity matrix and a latent low-dimensional embedding. Specifically, the similarity matrix to be learned is represented as a convex hull of similarity matrices from different views, where the nuclear norm is imposed to capture the principal information of multiple views and improve robustness against noise/outliers. Moreover, an effective low-dimensional representation is obtained by applying local embedding on the similarity matrix, which preserves the local intrinsic structure of data through dimensionality reduction. With these techniques, we formulate the MVJL as a joint optimization problem and derive its mathematical solution with the alternating direction method of multipliers strategy and the proximal gradient descent method. The solution, which consists of a similarity matrix and a low-dimensional representation, is ultimately integrated with spectral clustering or K-means for multi-view clustering. Extensive experimental results on real-world datasets demonstrate that MVJL achieves superior clustering performance over other state-of-the-art methods.

A Genetically Encoded Two-Dimensional Infrared Probe for Enzyme Active-Site Dynamics.

While two-dimensional infrared (2D-IR) spectroscopy is uniquely suitable for monitoring femtosecond (fs) to picosecond (ps) water dynamics around static protein structures, its utility for probing enzyme active-site dynamics is limited due to the lack of site-specific 2D-IR probes. We demonstrate the genetic incorporation of a novel 2D-IR probe, m-azido-L-tyrosine (N3Y) in the active-site of DddK, an iron-dependent enzyme that catalyzes the conversion of dimethylsulfoniopropionate to dimethylsulphide. Our results show that both the oxidation of active-site iron to FeIII , and the addition of denaturation reagents, result in significant decrease in enzyme activity and active-site water motion confinement. As tyrosine residues play important roles, including as general acids and bases, and electron transfer agents in many key enzymes, the genetically encoded 2D-IR probe N3Y should be broadly applicable to investigate how the enzyme active-site motions at the fs-ps time scale direct reaction pathways to facilitating specific chemical reactions.

Genetic Incorporation of Selenotyrosine Significantly Improves Enzymatic Activity of Agrobacterium radiobacter Phosphotriesterase.

Tyrosine plays important roles in many enzymes. To facilitate enzyme design, mechanistic studies and minimize structural perturbation in the active site, here we report the genetic incorporation of a novel unnatural amino acid selenotyrosine (SeHF), which has single-atom replacement in comparison to tyrosine. The arPTE-(Agrobacterium radiobacter Phosphotriesterase) Tyr309SeHF mutant exhibits a significant 12-fold increase in kcat and 3.2-fold enhancement in kcat /KM at pH 7.0. Molecular dynamics simulations show that the SeHF309 mutation results in a conformational switch which opens up the product release pocket and increases the product release rate, thereby elevating the overall enzyme activity. Significant improvement of the catalytic efficiency at neutral pH by single unnatural amino acid (UAA) mutation broadens the application of this enzyme, and provides valuable insights to the mechanism. Our method represents a new approach for designing enzymes with enhanced activity.

Multi-View Data Fusion Oriented Clustering via Nuclear Norm Minimization.

Image clustering remains challenging when handling image data from heterogeneous sources. Fusing the independent and complementary information existing in heterogeneous sources together facilitates to improve the image clustering performance. To this end, we propose a joint learning framework of multi-view image data fusion and clustering based on nuclear norm minimization. Specifically, we first formulate the problem as matrix factorization to a shared clustering indicator matrix and a representative coefficient matrix. The former is constrained with orthogonality and nonnegativity, which ensures the validation of clustering assignments. The latter is imposed with nuclear norm minimization to achieve compression of principal components for performance improvement. Then, an alternating minimization strategy is employed to efficiently decompose the multi-variable optimization problem into several small solvable sub-problems with closed-form solutions. Extensive experimental results on real-world image and video datasets demonstrate the superiority of proposed method over other state-of-the-art methods.

Empirically derived dietary patterns and constipation among a middle-aged population from China, 2016-2018.

BACKGROUND: The association of dietary patterns with constipation is not well established, particularly in Chinese population. Therefore, the present study aimed to determine the relationship between dietary patterns and the risk of constipation in a middle-aged Chinese population. METHODS: A total of 2267 participants aged 45-59 years were recruited in Hangzhou city, the capital of Zhejiang Province, east China from August 2016 to October 2018. Dietary intake was estimated using a semi-quantitative food frequency questionnaire (FFQ) containing 138 food items. Constipation was defined using the Rome II criteria. Multivariate logistic regression was used to examine the association between dietary patterns and the risk of constipation. RESULTS: Three major dietary patterns were extracted by factor analysis and labeled as the traditional southern Chinese, Western and grains-vegetables patterns. The prevalence of constipation in our study population was 13.28%. Compared with the participants in the lowest quartile, the participants in the highest quartile of the traditional southern Chinese pattern were associated with reduced odds of constipation (odd ratios (OR) = 0.79; 95%confidence interval (CI): 0.626-0.981; P < 0.05), after adjusting for confounding variables. In contrast, we found no significant associations between the Western and grains-vegetables patterns and the risk of constipation (P > 0.05). CONCLUSIONS: Our study demonstrated that the traditional southern Chinese pattern was associated with a reduced risk of constipation. Further longitudinal studies are needed to confirm our findings.

S-Click Reaction for Isotropic Orientation of Oxidases on Electrodes to Promote Electron Transfer at Low Potentials.

Electrochemical sensors are essential for point-of-care testing (POCT) and wearable sensing devices. Establishing an efficient electron transfer route between redox enzymes and electrodes is key for converting enzyme-catalyzed reactions into electrochemical signals, and for the development of robust, sensitive, and selective biosensors. We demonstrate that the site-specific incorporation of a novel synthetic amino acid (2-amino-3-(4-mercaptophenyl)propanoic acid) into redox enzymes, followed by an S-click reaction to wire the enzyme to the electrode, facilitates electron transfer. The fabricated biosensor demonstrated real-time and selective monitoring of tryptophan (Trp) in blood and sweat samples, with a linear range of 0.02-0.8 mm. Further developments along this route may result in dramatic expansion of portable electrochemical sensors for diverse health-determination molecules.

The Prognostic and Clinical Value of CD44 in Colorectal Cancer: A Meta-Analysis.

Background: CD44 is widely used as a putative cancer stem cells (CSCs) marker for colorectal cancer (CRC). However, the prognostic role of CD44 in CRC remains controversial. Methods: We performed a systematic review and meta-analysis to evaluate the association of various CD44 isoforms and overall survival (OS) and clinicopathological features of CRC patients. Results: A total of 48 studies were included in the meta-analysis. Total CD44 isoforms overexpression was significantly correlated with worse OS of patients with CRC (HR = 1.32, 95% CI = 1.08-1.61, P = 0.007). In a stratified analysis, a higher level of either CD44v6 or CD44v2 had an unfavorable impact on OS (HRCD44v6 = 1.50, 95% CI = 1.10-2.14, P = 0.010; HRCD44v2 = 2.93, 95% CI = 1.49-5.77, P = 0.002). Additionally, CD44 was shown to be associated with some clinicopathological features, such as lymph node metastasis (ORCD44 = 1.56, 95% CI = 1.01-2.41, P = 0.044; ORCD44v6 = 1.97, 95% CI = 1.19-3.26, P = 0.008; ORTotal CD44 isoforms = 1.57, 95% CI = 1.15-2.14, P = 0.004), distant metastasis (ORCD44 = 2.90, 95% CI = 1.08-7.83, P = 0.035; ORTotal CD44 isoforms = 1.89, 95% CI = 1.02-3.53, P = 0.044). Moreover, a high level of CD44 showed a possible correlation with poor differentiation (ORTotal CD44 isoforms = 1.44, 95% CI = 1.00-2.08, P = 0.051), elevated level of CD44v6 tend to be correlated with tumor size (OR = 1.71, 95% CI = 0.99-2.96, P = 0.056). Conclusions: This meta-analysis demonstrated that CD44 overexpression might be an unfavorable prognostic factor for CRC patients and could be used to predict poor differentiation, lymph node metastasis and distant metastasis.