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Prostate cancer is recognized as one of the most common tumors among men worldwide, yet the molecular mechanisms underlying its progression remain to be fully understood. In this study, we explored the role of interleukin-1 receptor-associated kinase 2 (IRAK2) in the progression of prostate cancer. We discovered that IRAK2 expression is downregulated in prostate cancer tissues and cells. Functional assays, including MTT, transwell assays, wound healing assays, and in vivo xenograft models, demonstrated that upregulation of IRAK2 significantly inhibited prostate cancer cell viability, migration, invasion, and tumor growth. Furthermore, we found that IRAK2 modulates the biological functions of prostate cancer by interacting with TNF receptor-associated factor 6 (TRAF6). Knockdown of TRAF6 reversed the suppressive effects of IRAK2 overexpression on prostate cancer cell progression. Additionally, IRAK2 was found to suppress the ubiquitination and degradation of TRAF6 in prostate cancer cells. IRAK2 also influenced the sensitivity of prostate cancer cells to docetaxel (DTX), and silencing IRAK2 reversed the anti-tumor effects of DTX on prostate cancer cells. Our findings suggest that IRAK2 functions as a tumor suppressor in prostate cancer and may serve as a potential therapeutic target for developing effective treatments for prostate cancer., Competing Interests: Declaration of competing interest All authors in this study declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

The preoperative diagnosis and management of Peutz-Jeghers syndrome (PJS) patients with cervical lesions remain problematic. This study analysed the associations between pathological types of cervical lesions in PJS patients and their MRI features. A total of 34 PJS patients were included and two experienced radiologists reviewed the MRIs independently. Based on the pathological diagnosis, the patients were categorized into four groups: normal (n  =  4), lobular endocervical glandular hyperplasia (LEGH, n  =  11), atypical LEGH (aLEGH, n  =  8), and gastric-type endocervical adenocarcinoma (G-EAC, n  =  11). By observing the MRI features, we found statistically significant differences in the extent of lesions (P  = 0 .001), distribution of microcysts (P  = 0 .001), proportion of microcysts (P  <  0.001) and endometrial involvement (P  = 0.019) among the four groups. Notably, solid components and disrupted cervical stromal rings were found only in the aLEGH and G-EAC groups (P  < 0.001).  Consequently, we created a novel grading system based on the aforementioned MRI features to align with the potential malignancy of cervical lesions in PJS patients. This system enables patients to receive timely and appropriate treatment recommendations while facilitating collaboration between radiologists and physicians., (© 2024. The Author(s).)

Microglial activation plays a crucial role in the disease progression in amyotrophic lateral sclerosis (ALS). Interleukin receptor-associated kinases-M (IRAK-M) is an important negative regulatory factor in the Toll-like receptor 4 (TLR4) pathway during microglia activation, and its mechanism in this process is still unclear. In the present study, we aimed to investigate the dynamic changes of IRAK-M and its protective effects for motor neurons in SOD1-G93A mouse model of ALS. qPCR (Real-time Quantitative PCR Detecting System) were used to examine the mRNA levels of IRAK-M in the spinal cord in both SOD1-G93A mice and their age-matched wild type (WT) littermates at 60, 100 and 140 days of age. We established an adeno-associated virus 9 (AAV9)-based platform by which IRAK-M was targeted mostly to microglial cells to investigate whether this approach could provide a protection in the SOD1-G93A mouse. Compared with age-matched WT mice, IRAK-M mRNA level was elevated at 100 and 140 days in the anterior horn region of spinal cords in the SOD1-G93A mouse. AAV9-IRAK-M treated SOD1-G93A mice showed reduction of IL-1β mRNA levels and significant improvements in the numbers of spinal motor neurons in spinal cord. Mice also showed previously reduction of muscle atrophy. Our data revealed the dynamic changes of IRAK-M during ALS pathological progression and demonstrated that an AAV9-IRAK-M delivery was an effective and translatable therapeutic approach for ALS. These findings may help identify potential molecular targets for ALS therapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the protective effects and mechanisms of targeted inhibition of type 3 deiodinase (Dio3) on skeletal muscle mitochondria in sepsis., Methods: (1) In vivo experiments: adeno-associated virus (AAV) was employed to specifically target Dio3 expression in the anterior tibial muscle of rats, and a septic rat model was generated using cecal ligation and puncture (CLP). The male Sprague-Dawley (SD) rats were divided into shNC+Sham group, shD3+Sham group, shNC+CLP group, and shD3+CLP group by random number table method, with 8 rats in each group. After CLP modeling, tibial samples were collected and Western blotting analysis was conducted to assess the protein levels of Dio3, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), and silence-regulatory protein 1 (SIRT1). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to examine mRNA expression of genes including thyroid hormone receptors (THRα, THRβ), monocarboxylate transporter 10 (MCT10), mitochondrial DNA (mtDNA), and PGC1α. Transmission electron microscopy was employed to investigate mitochondrial morphology. (2) In vitro experiments: involved culturing C2C12 myoblasts, interfering with Dio3 expression using lentivirus, and constructing an endotoxin cell model by treating cells with lipopolysaccharide (LPS). C2C12 cells were divided into shNC group, shD3 group, shNC+LPS group, and shD3+LPS group. Immunofluorescence colocalization analysis was performed to determine the intracellular distribution of PGC1α. Co-immunoprecipitation assay coupled with Western blotting was carried out to evaluate the acetylation level of PGC1α., Results: (1) In vivo experiments: compared with the shNC+Sham group, the expression of Dio3 protein in skeletal muscle of the shNC+CLP group was significantly increased (Dio3/β-Tubulin: 3.32±0.70 vs. 1.00±0.49, P < 0.05), however, there was no significant difference in the shD3+Sham group. Dio3 expression in the shD3+CLP group was markedly reduced relative to the shNC+CLP group (Dio3/β-Tubulin: 1.42±0.54 vs. 3.32±0.70, P < 0.05). Compared with the shNC+CLP group, the expression of T3-regulated genes in the shD3+CLP group were restored [THRα mRNA (2 -ΔΔCt ): 0.67±0.05 vs. 0.33±0.01, THRβ mRNA (2 -ΔΔCt ): 0.94±0.05 vs. 0.67±0.02, MCT10 mRNA (2 -ΔΔCt ): 0.65±0.03 vs. 0.57±0.02, all P < 0.05]. Morphology analysis by electron microscopy suggested prominent mitochondrial damage in the skeletal muscle of the shNC+CLP group, while the shD3+CLP group exhibited a marked improvement. Compared with the shNC+Sham group, the shNC+CLP group significantly reduced the number of mitochondria (cells/HP: 10.375±1.375 vs. 13.750±2.063, P < 0.05), while the shD3+CLP group significantly increased the number of mitochondria compared to the shNC+CLP group (cells/HP: 11.250±2.063 vs. 10.375±1.375, P < 0.05). The expression of mtDNA in shNC+CLP group was markedly reduced compared with shNC+Sham group (copies: 0.842±0.035 vs. 1.002±0.064, P < 0.05). Although no difference was detected in the mtDNA expression between shD3+CLP group and shNC+CLP group, but significant increase was found when compared with the shD3+Sham group (copies: 0.758±0.035 vs. 0.474±0.050, P < 0.05). In the shD3+CLP group, PGC1α expression was significantly improved at both transcriptional and protein levels relative to the shNC+CLP group [PGC1α mRNA (2 -ΔΔCt ): 1.49±0.13 vs. 0.68±0.06, PGC1α/β-Tubulin: 0.76±0.02 vs. 0.62±0.04, both P < 0.05]. (2) In vitro experiments: post-24-hour LPS treatment of C2C12 cells, the cellular localization of PGC1α became diffuse; interference with Dio3 expression promoted PGC1α translocation to the perinuclear region and nucleus. Moreover, the acetylated PGC1α level in the shD3+LPS group was significantly lower than that in the shNC+LPS group (acetylated PGC1α/β-Tubulin: 0.59±0.01 vs. 1.24±0.01, P < 0.05), while the expression of the deacetylating agent SIRT1 was substantially elevated following Dio3 inhibition (SIRT1/β-Tubulin: 1.04±0.04 vs. 0.58±0.03, P < 0.05). When SIRT1 activity was inhibited by using EX527, PGC1α protein expression was notably decreased compared to the shD3+LPS group (PGC1α/β-Tubulin: 0.92±0.03 vs. 1.58±0.03, P < 0.05)., Conclusions: Inhibition of Dio3 in skeletal muscle reduced the acetylation of PGC1α through activating SIRT1, facilitating nuclear translocation of PGC1α, thereby offering protection against sepsis-induced skeletal muscle mitochondrial damage.

Large-scale neural population recordings with single-cell resolution across the primate brain remain challenging. Here we introduce the Neuroscroll probe that isolates single neuronal activities simultaneously from 1,024 densely spaced channels that are flexibly distributed across the shank of the probe. The Neuroscroll probe length is easily tunable for individual probes from 10 mm to 90 mm, covering the brain size of non-human primates and humans, and the probes remain intact and functional after repeated bending deformations. The Neuroscroll probes provided reliable recordings from large neural populations with high chronic stability up to 105 weeks in rats. Recording with each Neuroscroll probe yielded hundreds of well-isolated single units simultaneously from multiple brain regions distributed across the entire depth of the rhesus macaque brain. With the thousand simultaneously recorded channels, unprecedented probe length, excellent mechanical stability and flexible recording site distribution, the Neuroscroll probes enable a wide range of new experimental paradigms in system neuroscience studies with great versatility., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background and Aims: Machine learning (ML) algorithms are widely applied in building models of medicine due to their powerful studying and generalizing ability. To assess the value of the Modified Computed Tomography Severity Index (MCTSI) combined with serological indicators for early prediction of severe acute pancreatitis (SAP) by automated ML (AutoML)., Patients and Methods: The clinical data, of the patients with acute pancreatitis (AP) hospitalized in Hospital 1 and hospital 2 from January 2017 to December 2021, were retrospectively analyzed. Serological indicators within 24 hours of admission were collected. MCTSI score was completed by noncontrast computed tomography within 24 hours of admission. Data from the hospital 1 were adopted for training, and data from the hospital 2 were adopted for external validation. The diagnosis of AP and SAP was based on the 2012 revised Atlanta classification of AP. Models were built using traditional logistic regression and AutoML analysis with 4 types of algorithms. The performance of models was evaluated by the receiver operating characteristic curve, the calibration curve, and the decision curve analysis based on logistic regression and decision curve analysis, feature importance, SHapley Additive exPlanation Plot, and Local Interpretable Model Agnostic Explanation based on AutoML., Results: A total of 499 patients were used to develop the models in the training data set. An independent data set of 201 patients was used to test the models. The model developed by the Deep Neural Net (DL) outperformed other models with an area under the receiver operating characteristic curve (areas under the curve) of 0.907 in the test set. Furthermore, among these AutoML models, the DL and gradient boosting machine models achieved the highest sensitivity values, both exceeding 0.800., Conclusion: The AutoML model based on the MCTSI score combined with serological indicators has good predictive value for SAP in the early stage., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Large-scale brain activity mapping is important for understanding the neural basis of behaviour. Electrocorticograms (ECoGs) have high spatiotemporal resolution, bandwidth, and signal quality. However, the invasiveness and surgical risks of electrode array implantation limit its application scope. We developed an ultrathin, flexible shape-changing electrode array (SCEA) for large-scale ECoG mapping with minimal invasiveness. SCEAs were inserted into cortical surfaces in compressed states through small openings in the skull or dura and fully expanded to cover large cortical areas. MRI and histological studies on rats proved the minimal invasiveness of the implantation process and the high chronic biocompatibility of the SCEAs. High-quality micro-ECoG activities mapped with SCEAs from male rodent brains during seizures and canine brains during the emergence period revealed the spatiotemporal organization of different brain states with resolution and bandwidth that cannot be achieved using existing noninvasive techniques. The biocompatibility and ability to map large-scale physiological and pathological cortical activities with high spatiotemporal resolution, bandwidth, and signal quality in a minimally invasive manner offer SCEAs as a superior tool for applications ranging from fundamental brain research to brain-machine interfaces., (© 2024. The Author(s).)

Background: Acute kidney injury (AKI) represents a frequent and grave complication associated with acute pancreatitis (AP), substantially elevating both mortality rates and the financial burden of hospitalization. The aim of our study is to construct a predictive model utilizing automated machine learning (AutoML) algorithms for the early prediction of AKI in patients with AP., Methods: We retrospectively analyzed patients who were diagnosed with AP in our hospital from January 2017 to December 2021. These patients were randomly allocated into a training set and a validation set at a ratio of 7:3. To develop predictive models for each set, we employed the least absolute shrinkage and selection operator (LASSO) algorithm along with AutoML. A nomogram was developed based on multivariate logistic regression analysis outcomes. The model's efficacy was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Additionally, the performance of the model constructed via AutoML was evaluated using decision curve analysis (DCA), feature importance, SHapley Additive exPlanations (SHAP) plots, and locally interpretable model-agnostic explanations (LIME)., Results: This study incorporated a total of 437 patients who met the inclusion criteria. Out of these, 313 were assigned to the training cohort and 124 to the validation cohort. In the training and validation cohorts, AKI occurred in 68 (21.7%) and 29(23.4%) patients, respectively. Comparative analysis revealed that the AutoML models exhibited enhanced performance over traditional logistic regression (LR). Furthermore, the deep learning (DL) model demonstrated superior predictive accuracy, evidenced by an area under the ROC curve of 0.963 in the training set and 0.830 in the validation set, surpassing other comparative models. The key variables identified as significant in the DL model within the training dataset included creatinine (Cr), urea (Urea), international normalized ratio (INR), etiology, smoking, alanine aminotransferase (ALT), hypertension, prothrombin time (PT), lactate dehydrogenase (LDH), and diabetes., Conclusion: The AutoML model, utilizing DL algorithm, offers considerable clinical significance in the early detection of AKI among patients with AP., (© 2024. The Author(s).)

As natural adjuvants, the bacterial outer membrane vesicles (OMV) hold great potential in cancer vaccines. However, the inherent immunotoxicity of OMV and the rarity of tumor-specific antigens seriously hamper the clinical translation of OMV-based cancer vaccines. Herein, metal-phenolic networks (MPNs) are used to attenuate the toxicity of OMV, meanwhile, provide tumor antigens via the chemodynamic effect induced immunogenic cell death (ICD). Specifically, MPNs are assembled on the OMV surface through the coordination reaction between ferric ions and tannic acid. The iron-based "prison" is locally collapsed in the tumor microenvironment (TME) with both low pH and high ATP features, and thus the systemic toxicity of OMV is significantly attenuated. The released ferric ions in TME promote the ICD of cancer cells through Fenton reaction and then the generation of abundant tumor antigens, which can be used to fabricate in-situ vaccines by converging with OMV. Together with the immunomodulatory effect of OMV, potent tumor repression on a bilateral tumor model is achieved with good biosafety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Nitrite (NO 2 - ) is an inorganic contaminant that exists widely in the environment including water and food products, excessive amounts of NO 2 - would threaten humans and aquatic life. Developing a rapid and convenient sensing method for NO 2 - remains a great challenge. Herein, a colorimetric and near-infrared fluorescent probe (TBM) was synthesized and applied for sensitively and selectively detecting NO 2 - in water, food samples and Escherichia coli (E. coli). With the addition of NO 2 - , the probe TBM solution has a distinct visual color changed from red to colorless and fluorescence intensity at 620 nm quickly decreased. The probe TBM could detect NO 2 - quantitatively with a detection limit of 85 nM based on a 3σ/slope. Under optimum conditions, TBM has been successfully used to detect NO 2 - in real-world environmental and dietary samples, with positive results. Besides, paper strips loaded with TBM have been used to visually determine NO 2 - levels. Most importantly, TBM has also been proven to be able to discriminate from different concentrations of NO 2 - in E. coli by fluorescence imaging. In summary, the probe TBM was successfully developed for the accurate quantification, naked eyes detection and bioimaging of NO 2 - in water, food samples and E. coli, which provides a useful tool to better guarantee the quality and safety of daily life and food industry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Biological receptor-ligand adhesion governed by mammalian cells involves a series of mechanochemical processes that can realize reversible, loading rate-dependent specific interfacial bonding, and even exhibit a counterintuitive behavior called catch bonds that tend to have much longer lifetimes when larger pulling forces are applied. Inspired by these catch bonds, we designed a hydrogen bonding-meditated hydrogel made from acrylic acid-N-acryloyl glycinamide (AA-NAGA) copolymers and tannic acids (TA), which formed repeatable specific adhesion to polar surfaces in an ultra-fast and robust way, but hardly adhered to nonpolar materials. It demonstrated up to five-fold increase in shear adhesive strength and interfacial adhesive toughness with external loading rates varying from 5 to 500 mm min -1 . With a mechanochemical coupling model based on Monte Carlo simulations, we quantitatively revealed the nonlinear dependence of rate-sensitive interfacial adhesion on external loading, which was in good agreement with the experimental data. Likewise, the developed hydrogels were biocompatible, possessed antioxidant and antibacterial properties and promoted wound healing. This work not only reports a stimuli-responsive hydrogel adhesive suitable for multiple biomedical applications, but also offers an innovative strategy for bionic designs of smart hydrogels with loading rate-sensitive specific adhesion for various emerging areas including flexible electronics and soft robotics., Competing Interests: The authors declare that there is no conflict of interest in this manuscript., (© 2022 The Authors.)

Nicotinamide mononucleotide (NMN) exerts physiological effects in mammals through its conversion to nicotinamide adenine dinucleotide (NAD + ). In this study, we established experimental models of colitis by mixing drinking water of C57BL/6J mice with dextran sodium sulphate (DSS), and then fed them with the same concentration of NMN or at the same time. After NMN treatment, we observed improved morphology of inflamed intestines, slightly restored length of colon, improved barrier function and reduced proinflammatory factors expression in serum. Also, significant alterations in the composition and abundance of intestinal flora in IBD mice were found. The abundance of Firmicutes , Verrucomicrobia , Akkermansia and Lactobacillus , considered as beneficial bacteria, increased, while Bacteroidetes and Muribaculaceae unclassifiably decreased. Taken together, these results suggest that NMN may improve intestinal inflammation, reduce intestinal mucosal permeability and repair gut flora dysbiosis in IBD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier B.V.)

Extracellular vesicles (EVs) exhibiting versatile biological functions provide promising prospects as natural therapeutic agents and drug delivery vehicles. For future clinical translation, revealing the fate of EVs in vivo, especially their accumulation at lesion sites, is very important. The continuous development of in vivo imaging technology has made it possible to track the real-time distribution of EVs. This article reviews the applications of mammal-, plant-, and bacteria-derived EVs in tumor therapy, the labeling methods of EVs for in vivo imaging, the advantages and disadvantages of different imaging techniques, and possible improvements for future work., (© 2022 The Authors. Published by Wiley-VCH GmbH.)

Aldolase A (A-2) (ALD), Kelch-like-ECH associated protein-1 (Keap-1), and Forkhead box O4 (FoxO4) are key regulatory proteins, which have been proven to be involved in tumor development. However, the clinicopathological significance of ALD, Keap-1, and FoxO4 expressions in colorectal (colon) carcinoma (CRC) is not clearly known. We sought to explore the clinicopathological significance of ALD, Keap-1, and FoxO4 in CRC to provide evidences for potential monitoring index of CRC. Cases of 199 CRC patients were analyzed retrospectively. Evaluation of ALD, cAMP response element-binding protein-2, cyclo-oxygenase 2, FoxO4, Keap-1, and p53 expressions in CRC patients was accomplished with immunohistochemical technique. The patients were divided into negative and positive groups in accordance with immunohistochemical result. We compared the clinicopathological characteristics of the patients in the 2 groups, coupled with analysis of the relationship between 6 aforesaid proteins and clinicopathological characteristics. Herein, we confirmed the association of tumor location with the expression of ALD, Keap-1, and FoxO4. Also, tumor differentiation was observed to associate significantly with the expression of Keap-1, FoxO4, and Cox-2. The data also revealed that there was a correlation between smoking and expression of ALD, Keap-1, FoxO4, p53, and Cox-2. Nevertheless, insignificant difference was observed when clinicopathological characteristics were compared with cAMP response element-binding protein-2 expression. These findings suggest that ALD, Keap-1, and FoxO4 reinvolved in CRC development, and thus may be considered as potential monitoring protein for CRC., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Urban and regional ozone (O 3 ) pollution is a public health concern and causes damage to ecosystems. Due to the diverse emission sources of O 3 precursors and the complex interactions of air dispersion and chemistry, identifying the contributing sources of O 3 pollution requires integrated analysis to guide emission reduction plans. In this study, the meteorological characteristics leading to O 3 polluted days (in which the maximum daily 8-h average O 3 concentration is higher than the China Class II National O 3 Standard (160 μg/m 3 )) in Guangzhou (GZ, China) were analyzed based on data from 2019. The O 3 formation regimes and source apportionments under various prevailing wind directions were evaluated using a Response Surface Modeling (RSM) approach. The results showed that O 3 polluted days in 2019 could be classified into four types of synoptic patterns (i.e., cyclone, anticyclone, trough, and high pressure approaching to sea) and were strongly correlated with high ambient temperature, low relative humidity, low wind speed, variable prevailing wind directions. Additionally, the cyclone pattern strongly promoted O 3 formation due to its peripheral subsidence. The O 3 formation was nitrogen oxides (NO x )-limited under the northerly wind, while volatile organic compounds (VOC)-limited under other prevailing wind directions. Anthropogenic emissions contributed largely to the O 3 formation (54-78%) under the westerly, southwesterly, easterly, southeasterly, or southerly wind, but only moderately (35-47%) under the northerly or northeasterly wind. Furthermore, as for anthropogenic contributions, local emission contributions were the largest (39-60%) regardless of prevailing wind directions, especially the local NO x contributions (19-43%); the dominant upwind regional emissions contributed 12-46% (e.g., contributions from Dongguan were 12-20% under the southeasterly wind). The emission control strategies for O 3 polluted days should focus on local emission sources in conjunction with the emission reduction of upwind regional sources., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Recent studies have proposed that pyruvate dehydrogenase E1 component subunit alpha (PDHA1), a cuproptosis-key gene, is crucial to the glucose metabolism reprogram of tumor cells. However, the functional roles and regulated mechanisms of PDHA1 in multiple cancers are largely unknown. The Cancer Genome Atlas (TCGA), GEPIA2, and cBioPortal databases were utilized to elucidate the function of PDHA1 in 33 tumor types. We found that PDHA1 was aberrantly expressed in most cancer types. Lung adenocarcinoma (LUAD) patients with high PDHA1 levels were significantly correlated with poor prognosis of overall survival (OS) and first progression (FP). Kidney renal clear cell carcinoma (KIRC) patients with low PDHA1 levels displayed poor OS and disease-free survival (DFS). However, for stomach adenocarcinoma (STAD), the downregulated PDHA1 expression predicted a good prognosis in patients. Moreover, we evaluated the mutation diversity of PDHA1 in cancers and their association with prognosis. We also analyzed the protein phosphorylation and DNA methylation of PDHA1 in various tumors. The PDHA1 expression was negatively correlated with tumor-infiltrating immune cells, such as myeloid dendritic cells (DCs), B cells, and T cells in pan-cancers. Mechanically, we used single-cell sequencing to discover that the PDHA1 expression had a close link with several cancer-associated signaling pathways, such as DNA damage, cell invasion, and angiogenesis. At last, we conducted a co-expressed enrichment analysis and showed that aberrantly expressed PDHA1 participated in the regulation of mitochondrial signaling pathways, including oxidative phosphorylation, cellular respiration, and electron transfer activity. In summary, PDHA1 could be a prognostic and immune-associated biomarker in multiple cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Deng, Jiang, Zeng, Peng and Song.)

Cancer vaccines are emerging as an attractive modality for tumor immunotherapy. However, their practical application is seriously impeded by the complex fabrication and unsatisfactory outcomes. Herein, we construct bacterial outer membrane vesicles (OMVs)-based in situ cancer vaccine with phytochemical features for photodynamic effects-promoted immunotherapy. By simply fusing thylakoid membranes with OMVs, bacteria-plant hybrid vesicles (BPNs) are prepared. After systemic administration, BPNs can target tumor tissues and stimulate the activation of immune cells, including dendritic cells (DCs). The photodynamic effects derived from thylakoid lead to the disruption of local tumors and then the release of tumor-associated antigens that are effectively presented by DCs, inducing remarkable tumor-specific CD8 + T cell responses. Moreover, BPNs can efficiently ameliorate the immunosuppressive tumor microenvironment and further boost immune responses. Therefore, both tumor development and metastasis can be efficiently prevented. This work provides a novel idea for developing a versatile membrane-based hybrid system for highly efficient tumor treatment.

Ovarian aging affects the reproductive health of elderly women due to decline in oocyte quality, which is closely related to mitochondrial dysfunction. Nicotinamide mononucleotide (NMN), as a precursor of NAD + , effectively regulate mitochondria metabolism in mice. However, roles of NMN in improving age-related diminished ovary reserve remain to be determined. In present study, 4, 8, 12, 24, 40-week old female ICR mice were collected and a 20-week-long administration of NMN was conducted to 40-week-old mice (60WN), meanwhile the control group is given water (60WC). First, we found that 20-week-long administration of NMN to 40-week-old mice exhibited anti-aging and anti-inflammatory effects on organ structures, along with the improvement of estrus cycle condition and endocrine function. The number of primordial, primary, secondary, antral follicles and corpora luteum of ovaries in 60WN group was significantly increased compared with those in 60WC group. Additionally, the protein and gene expressions of P16 of ovaries were significantly reduced in 60WN group than in 60WC group. the mitochondria biogenesis, autophagy level, and proteases activity enhanced in granulosa cells after 20-week-administration of NMN. Present results indicate that NMN has the potential to save diminished ovary reserve by long-term treatment, providing a basis for exploring the role of NMN in anti-ovarian aging by enhancing the mitophagy level of granulosa cells., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Research on social public opinion of new media is currently an important interdisciplinary topic in the international academic community. Under the background of COVID-19, the major public health event of in China, this research took social workers as the research object who worked during the period of epidemic prevention and control. It referred to the international research on public opinion and selected 63 related hotly discussed articles and public comments on the WeChat public platform, the new Chinese Internet media. Moreover, the research conducted text mining on related public opinion with the 5 W communication model from public opinion evolution, text content, communication media, audiences, and public opinion influence, and used grounded theory building a development model of the generation of network public opinion. It also put forward the development needs of social work in the aspects of community resilience, social work practice, lack of public health social workers, and big data warning, etc., and pointed out that social work lacks its proper structural status in China's public health system and emergency management system.

The aim of this study was to determine the effects of long-term Nicotinamide mononucleotide (NMN) treatment on modulating gut microbiota diversity and composition, as well as its association with intestinal barrier function. In this study, C57BL/6J mice were fed different concentrations of NMN, and their feces were collected for detection of 16S rDNA and non-targeted metabolites to explore the effects of NMN on intestinal microbiota and metabolites. The results revealed that NMN increased the abundance of butyric acid-producing bacteria (Ruminococcae&#95;UCG-014 and Prevotellaceae&#95;NK3B31&#95;group) and other probiotics (Akkermansia muciniphila), while the abundance of several harmful bacteria (Bilophila and Oscillibacter) were decreased after NMN treatment. Meanwhile, the level of bile acid-related metabolites in feces from the G1 group (0.1 mg/ml) was significantly increased compared to the control group, including cholic acid, taurodeoxycholic acid, taurocholic acid, glycocholic acid, and tauro-β-muricholic acid. In addition, long-term NMN treatment affected the permeability of the intestinal mucosa. The number of goblet cells and mucus thickness increased, as well as expression of tight junction protein. These results demonstrate that NMN reduced intestinal mucosal permeability and exerts a protective effect on the intestinal tract. This study lays the foundation for exploring NMN's utility in clinical research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Jiang, Wang, Zhou, Tang, Ren, Qian, Zhou and Gong.)

Introduction: Turns-amplitude, number of small segments (NSS)-activity, and envelope-activity clouds are three methods of electromyography (EMG) interference pattern analysis. Our objective was to evaluate the sensitivity and specificity of each individual cloud analysis and combined clouds analysis to compare with that of quantitative motor unit potential (QMUP) analysis., Methods: A total of 379 muscles from 100 patients were analyzed by both QMUP and clouds analyses. Calculation of sensitivity and specificity was based on the clinical diagnosis as the "gold standard.", Results: For discrimination of abnormal vs normal and neuropathic vs non-neuropathic, combined clouds analysis had greater sensitivity than QMUP analysis and any single cloud analysis, but there were no differences in specificity. For discrimination of myopathic vs non-myopathic, combined clouds analysis and single cloud analysis had greater sensitivity than QMUP analysis, but there were no differences in specificity., Discussion: Combined clouds analysis was superior to QMUP and each single cloud analysis for distinguishing normal, myopathic, and neuropathic muscles., (© 2020 Wiley Periodicals LLC.)

Photoperiodic flowering responses are classified into three major types: long day (LD), short day (SD), and day neutral (DN). The inverse responses to daylength of LD and SD plants have been partly characterized in Arabidopsis and rice; however, the molecular mechanism underlying the DN response is largely unknown. Modern roses are economically important ornamental plants with continuous flowering (CF) features, and are generally regarded as DN plants. Here, RcCO and RcCOL4 were identified as floral activators up-regulated under LD and SD conditions, respectively, in the CF cultivar Rosa chinensis 'Old-Blush'. Diminishing the expression of RcCO or/and RcCOL4 by virus-induced gene silencing (VIGS) delayed flowering time under both SDs and LDs. Interestingly, in contrast to RcCO-silenced plants, the flowering time of RcCOL4-silenced plants was more delayed under SD than under LD conditions, indicating perturbed plant responses to day neutrality. Further analyses revealed that physical interaction between RcCOL4 and RcCO facilitated binding of RcCO to the CORE motif in the promoter of RcFT and induction of RcFT. Taken together, the complementary expression of RcCO in LDs and of RcCOL4 in SDs guaranteed flowering under favorable growth conditions regardless of the photoperiod. This finding established the molecular foundation of CF in roses and further shed light on the underlying mechanisms of DN responses., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Number of small segments (NSS) and activity analysis is a mature method for electromyographic automatic interference pattern analysis (IPA), but there are few reports on the application of this technique. Our objective was to establish normal reference values of NSS-activity clouds., Methods: The NSS and activity data of the sternocleidomastoid, deltoid, biceps brachii (long head), extensor digitorum communis, abductor digiti minimi, vastus medialis, tibialis anterior, and gastrocnemius (lateral head) muscles were obtained from 34 men and 25 women, aged 15-80 years, using concentric needle electrodes. A linear regression of log(NSS) vs log(activity) was performed and the slope, intercept and standard deviation were calculated for each muscle. These variables were transformed back to the original parameters to yield clouds., Results: Normal NSS-activity clouds for the above eight muscles were obtained., Conclusions: Normal reference values of NSS-activity may facilitate detection of early and mild neurogenic and myogenic abnormalities., (© 2020 Wiley Periodicals, Inc.)

Stress-induced gastric ulcer is one of the common complications affecting patients after trauma, mainly leading to gastrointestinal bleeding and perforation, and severe cases may be life-threatening. However, the molecular mechanism of stress-induced gastric ulcer remains unclear. In the present study, RNA-sequencing was performed on gastric tissues of normal rats (C), stress-induced gastric ulcer rats (T0), and rats recovered from gastric ulcer for 3 days (T3), and bioinformatics analysis was performed to determine changes in gene expression and biological pathways. The protein-protein interaction (PPI) networks of differentially expressed genes (DEGs) were constructed by STRING and visualized by the Cytoscape software. The associated transcriptional factor (TFs)-gene regulatory network of the hub DEGs was also constructed. Pairwise comparisons obtained 103 (T0&#95;C), 127 (T3&#95;T0), and 13 (T3&#95;C) DEGs, respectively. Gene ontology (GO) enrichment analysis indicated DEGs in T0&#95;C and T3&#95;T0 were significantly enriched in response to oxygen-containing compound, response to organic substance, and response to external stimulus. Pathway analysis suggested that DEGs were enriched in TNF signaling pathway, PPAR signaling pathway, apoptosis, and IL-17 signaling pathway. Seven hub genes (Fos, Jun, Nfkbia, Dusp1, Pim3, Junb, and Fosb) were obtained from the PPI networks of T0&#95;C and T3&#95;T0. Key TFs with close interactions, such as Fos, Jun, Nfkbia, Junb, Egr1, and Fosb, were screened This study used RNA-sequencing and bioinformatics analysis to screen out genes associated with gastric ulcer, which can help reveal the molecular mechanism of gastric ulcer development and restoration, and provide reference for the treatment of human gastric ulcers.

Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano-bioconjugates for cancer therapy. Azide-modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne-modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH-sensitive linkers. After systemic administration, the nano-bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic-imine bonds of the nano-bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished "don't eat me" signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro-tumoral M2 to anti-tumoral M1., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multifunctional nanomaterials for dual-mode imaging guided cancer therapy are highly desirable in clinical applications. Herein, a flowerlike NiS 2 -coated NaLuF 4 :Nd (Lu:Nd@NiS 2 ) nanoparticle was synthesized as a novel therapeutic agent for short-wave infrared light imaging and magnetic resonance imaging to guide photothermal therapy (PTT). The material was then loaded with phenolic epigallocatechin 3-gallate (EGCG), which is a natural heat-shock protein 90 (HSP90) inhibitor. Upon near infrared irradiation, EGCG was released from the Lu:Nd@NiS 2 -EGCG, which bound HSP90 and reduced cell tolerance to heat, resulting in a better therapeutic effect at the same elevated temperature. Therefore, with minimal side effects and remarkable antitumor efficacy in vivo, Lu:Nd@NiS 2 -EGCG appeared to be a promising photothermal agent for enhanced PTT.

Using metal oxide semiconductor nanomaterials for synergistic cancer treatment has recently attracted the attention of numerous researchers. Herein, oxygen-defective vanadium oxide nanodots (VO x NDs) with ultra-small size and great dispersibility were synthesized via a novel user-friendly method, and then doxorubicin was loaded onto the VO x NDs surfaces. The VO x NDs had great photothermal conversion efficiency and stability. Doxorubicin-loaded VO x NDs can simultaneously serve as therapeutic agent and tumor microenvironment-activable HSP60 inhibitor, resulting in improved efficacy of photothermal therapy and released active doxorubicin for chemotherapy. Finally, we show that synergistic treatment achieved significant therapeutic effects in mice. These results provided a promising strategy for developing novel methods of synthesizing metal oxide semiconductors for enhanced synergistic cancer treatment., (Copyright © 2018. Published by Elsevier Ltd.)

BACKGROUND It is well documented that the Blood-Brain barrier (BBB) can be damaged by matrix metalloproteases (MMPs) after intracerebral hemorrhage (ICH), but little is known about the mechanism of this effect. MATERIAL AND METHODS We established an ICH model in rats by injecting collagenase VII into the striatum. Afterwards, intraperitoneal injection of these rats with 40 mg/kg GM6001 (a MMPs inhibitor). The effects of GM6001 on ICH were investigated by neurological severity score, brain water content, Evans blue staining, hematoxylin-eosin staining, immunohistochemical staining, and Western blot assays. RESULTS We demonstrated that the neurological damage caused by ICH was relieved at 5 and 7 days following administration of GM6001. The impaired BBB induced by ICH was improved in response to GM6001 treatment at around 3 days, as evidenced by alleviated cerebral edema, decreased Evans blue extravasation, and a reduction in inflammatory cellular infiltration. Mechanism analysis revealed that ICH induced the generation of β-dystroglycan cleavage, which could be suppressed by GM6001 treatment. Furthermore, we found that recombinant MMP2 and MMP9 triggered the cleavage of β-dystroglycan in vitro, and this action could be inhibited by GM6001 administration. CONCLUSIONS Taken together, our results suggest that MMPs-mediated cleavage on β-dystroglycan may play an important role in BBB after ICH.

Lung injury is a hydrogen sulfide (H 2 S)-associated complication with high mortality in acute pancreatitis (AP) cases. Herein, we used Prussian Blue (PB) as a H 2 S-responsive acceptor to develop a novel pure-inorganic upconversion nanoprobe for detecting and eliminating H 2 S, which can be used for diagnosing AP and alleviating lung injury. Upconversion nanoprobes with 5 nm PB shells were optimized to achieve outstanding in vitro H 2 S detection capacity (linear range: 0-150 μM, LOD: 50 nM), which met the in vivo serum H 2 S range, and thus were feasible for imaging H 2 S in vivo . More importantly, when combined with the traditional H 2 S synthetase inhibitor dl-PAG, the nanoprobes also served as a therapeutic agent that synergistically alleviated lung injury. As PB is an FDA-approved drug, our work proposes a potential clinical modality for the early diagnosis of AP, which will decrease lung injury-induced mortality and increase the survival rates of AP cases.

Soil disinfestation is an important agricultural practice to conquer soil-borne diseases and thereby ensure crop productivity. Reductive soil disinfestation (RSD) had been developed as an environmentally friendly alternative to chemical soil disinfestation (CSD). However, the differences between CSD and RSD on soil-borne pathogen suppression and fungal community structure remain poorly understood. In this work, five treatments, i.e., untreated soil (CK), CSD with 0.5 t ha -1 dazomet (DZ), RSD with 10 t ha -1 ethanol (ET), 15 t ha -1 sugarcane bagasse (SB), and 15 t ha -1 bean dregs (BD), were performed to investigate their influences on disinfestation efficiency, fungal abundance, diversity, and community structure via quantitative PCR and high-throughput sequencing. RSD-related treatments, especially the BD treatment, effectively alleviated soil acidification and salinization. The fungal abundance and microbial activity considerably increased in the BD treatment and significantly declined in the DZ treatment as compared to the CK treatment. Moreover, both CSD and RSD-related treatments significantly inhibited the population of Fusarium oxysporum and the relative abundance of genus Fusarium. Fungal community structure was notably altered by CSD and RSD practices. Furthermore, both CSD and RSD harbored a distinct unique microbiome, with the DZ treatment dominated by the genus Mortierella and BD treatment predominated by the genera Zopfiella, Chaetomium, and Penicillium. Taken together, these results indicate that the BD treatment could considerably alleviate the soil deterioration, improve soil microbial activity, and reassemble a non-pathogen unique microbiome that have more disease-suppressive agents and thus might be a promising disinfestation practice to control soil-borne disease in monoculture system.

For many years, fluorosis has been known as a worldwide disease which seriously diminishes quality of life through skeletal embrittlement and hepatic damage. Aiming to develop novel drugs for simultaneous fluorosis diagnosis and therapy, in this work we explore the feasibility of a novel pyrogallic acid-titanium(iv) complex-modified upconversion nanoprobe (UCNP-PA-Ti) for F - capture and real-time quantification. Utilizing the strong interaction between Ti 4+ and F - , the modified PA-Ti decomposes in F - -containing solution, which not only weakens the FRET but results in upconversion luminescence (UCL) recovery. Both in vitro and in vivo experiments demonstrate a highly sensitive F - UCL response and therapeutic efficiency, which was promising for successful UCL image monitoring and the therapeutic process. Long blood circulation time and low toxicity ensured their safe application for fluorosis theranostics. Our work provides a new possibility for F - concentration detection within fluorosis therapeutic periods and encourages the development of novel drugs for fluorosis theranostics.

The development of novel and effective cancer treatments will greatly contribute to prolonging and improving patient lives. In this study, a multifunctional nanoplatform was designed and developed based on mesoporous NiO (mNiO) nanoparticles and terbium complexes as an artemisinin (ART) vehicle, a T 2 -weighted contrast agent, and a luminescence imaging probe. mNiO is a novel pH-responsive material that can degrade and release nickel ions (Ni 2+ ) in an acidic tumor microenvironment. The endoperoxide bridge bond in the structure of ART tends to react with Ni 2+ to produce radicals that can kill tumor cells. On the basis of its excellent near-infrared absorbance, mNiO can also be considered as a novel photothermal conversion agent for cancer photothermal therapy (PTT). Compared with free ART or PTT only, this novel agent showed remarkably enhanced antitumor activity in cultured cells and in tumor mice models, owing to the hypoxic tumor microenvironment impelling synergistic therapeutic action. These results provide a novel way of using a promising natural drug-based nanoplatform for synergistic therapy of tumors.

Oxidative stress, as an essential cause to many diseases via irreversible biomolecule oxidation, can be induced by casual-contacted nanomaterials, which can generate hydroxyl radical (•OH) due to their active surface capacity. Herein, we report a novel upconversion nanoprobe for ratiometric •OH detection and monitoring titanium oxide nanomaterial-induced oxidative stress. Unlike previously developed nanoprobes, the •OH-responsive acceptor in these nanoprobes can be rapidly prepared and easily recycled. With a detection limit of ∼2 nM and a broad linear range of 4 nM-16 μM, the nanoprobe is suitable for both in vitro and in vivo applications. The facile preparation and recyclable strategy provide a new method for developing novel nanoprobes that can directly detect hazardous molecules in biological samples and systems.

To achieve accurate tumor location and highly efficient cancer therapy effect, the properties of cancer theranostic agents should be optimized and enhanced. In this work, ultra-small Nd doped NaDyF 4 were firstly reported as novel contrast agents for near-infrared second window downconversion luminescence (NIR II DCL) and magnetic resonance imaging. Based on the optimization strategy, gallic acid-Fe(III) complex modified NaDyF 4 :10%Nd (NaDyF 4 :10%Nd-GA-Fe) was selected as the optimal agent with high transversal relaxivity, strong NIR II DCL, high photothermal conversion efficiency, and low toxicity. In vitro experiment found that it can be aggregated rapidly in low pH condition, leading to the particle size increasing. Due to the theranostic properties coupled in NaDyF 4 :10%Nd-GA-Fe are size dependent, properties enhancement was observed within the pH responsive aggregation progress. Further study in small animal model bearing tumor demonstrated the enhanced cancer theranostic by in situ aggregation. The optimized nanoagents have potential applications in medical and also provide a novel strategy for future study of cancer theranostic enhancement., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.