ADAMTS5 Promotes Permeability of the Blood-Brain Barrier during Treponema pallidum Subspecies pallidum Invading the Central Nervous System.

The pathogenesis of neurosyphilis remains unclear. A previous study found a noteworthy up-regulation of a disintegrin and metalloproteinase with thrombospondin type 1 motif 5 (ADAMTS5) gene in human brain microvascular endothelial cells cocultured with Treponema pallidum subspecies pallidum (Tp). To investigate the ADAMTS5 role in Tp invading the central nervous system (CNS), we conducted relevant experiments. Our study revealed that Tp caused an increase in human cortical microvascular endothelial cell/D3 (hCMEC/D3) barrier permeability and significantly enhanced ADAMTS5 expression. The heightened permeability of the hCMEC/D3 barrier was effectively mitigated by inhibiting ADAMTS5. During this process, Tp promoted interleukin-1ß production, which, in turn, facilitated ADAMTS5 expression. Furthermore, Tp significantly reduced the glycocalyx on the surface of hCMEC/D3 cells, which was also ameliorated by inhibiting ADAMTS5. Additionally, ADAMTS5 and endothelial glycocalyx components notably increased in the cerebrospinal fluid of HIV-negative neurosyphilis patients. This research provided the first demonstration of the ADAMTS5 role in Tp invading the CNS and offered new insight into neurosyphilis pathogenesis.

Genetically engineered macrophages as living cell drug carriers for targeted cancer therapy.

Precise targeting is a major prerequisite for effective cancer therapy because it ensures a sufficient therapeutic dosage in tumors while minimizing off-target side effects. Herein, we report a live-macrophage-based therapeutic system for high-efficiency tumor therapy. As a proof of concept, anti-human epidermal growth factor receptor-2 (HER2) affibodies were genetically engineered onto the extracellular membrane of macrophages (AE-Mφ), which further internalized doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) nanoparticles (NPs) to produce a macrophage-based therapeutic system armed with anti-HER2 affibodies. NPs(DOX)@AE-Mφ were able to target HER2+ cancer cells and specifically elicit affibody-mediated cell therapy. Most importantly, the superior HER2 + -targeting capability of NPs(DOX)@AE-Mφ greatly guaranteed high accumulation at the tumor site for improved chemotherapy, which acted synergistically with cell therapy to significantly enhance anti-tumor efficacy. This study suggests that NPs(DOX)@AE-Mφ could be utilized as an innovative 'living targeted drug' platform for combining both macrophage-mediated cell therapy and targeted chemotherapy for the individualized treatment of solid tumors.

A multi-omics approach to unravelling the coupling mechanism of nitrogen metabolism and phenanthrene biodegradation in soil amended with biochar.

The presence of polycyclic aromatic hydrocarbons (PAHs) in soil negatively affects the environment and the degradation of these contaminants is influenced by nitrogen metabolism. However, the mechanisms underlying the interrelationships between the functional genes involved in nitrogen metabolism and phenanthrene (PHE) biodegradation, as well as the effects of biochar on these mechanisms, require further study. Therefore, this study utilised metabolomic and metagenomic analysis to investigate primary nitrogen processes, associated functional soil enzymes and functional genes, and differential soil metabolites in PHE-contaminated soil with and without biochar amendment over a 45-day incubation period. Results showed that dissimilatory nitrate reduction to ammonium (DNRA) and denitrification were the dominant nitrogen metabolism processes in PHE-contaminated soil. The addition of biochar enhanced nitrogen modules, exhibiting discernible temporal fluctuations in denitrification and DNRA proportions. Co-occurrence networks and correlation heatmap analysis revealed potential interactions among functional genes and enzymes responsible for PHE biodegradation and nitrogen metabolism. Notably, enzymes associated with denitrification and DNRA displayed significant positive correlation with enzymes involved in downstream phenanthrene degradation. Of particular interest was stronger correlation observed with the addition of biochar. However, biochar amendment inhibited the 9-phenanthrol degradation pathway, resulting in elevated levels of glutathione (GSH) in response to environmental stress. These findings provide new insights into the interactions between nitrogen metabolism and PHE biodegradation in soil and highlight the dual effects of biochar on these processes.

In Situ Constructing Ultrafast Ion Channel for Promoting High-Rate Cycle Stability of Nano-Na3V2(PO4)3 Cathode.

Encapsulating nanomaterials in carbon is one of the main ways to increase the cathode stability, but it is difficult to simultaneously optimize the rate capacity and enhance durability derived from the insufficient ion transport channels and deficient ion adsorption sites that constipate the ion transport and pseudocapacitive reaction. Herein, we develop the ligand-confined growth strategy to encapsulate the nano-Na3V2(PO4)3 cathode material in various carbon channels (microporous, mesoporous, and macroporous) to discriminate the optimal carbon channels for synchronously improving rate capacity and holding the high-rate cycle stability. Benefiting from the unobstructed ion/charge transport channels and flexible maskant created by the interconnected mesoporous carbon channels, the prepared Na3V2(PO4)3 nanoparticles confined in mesoporous carbon channel (Mes-NVP/C) achieve a discharge-specific capacity of 70 mAh g-1 even at the ultrahigh rate of 100 C, higher than those of the Na3V2(PO4)3 nanoparticles confined in microporous and macroporous carbon channel (Micr-NVP/C and Macr-NVP/C), respectively. Significantly, the capacity retention rate of Mes-NVP/C after 5000 cycles at 20 C is as high as 90.48%, exceeding most of the reported work. These findings hold great promise for traditional cathode materials to synergistically realize fast charging ability and long cycle life.

Prognostic value of oxidative stress-related genes in colorectal cancer and its correlation with tumor immunity.

Oxidative stress (OS) plays an essential role in chronic diseases such as colorectal cancer (CRC). In this study, we aimed to explore the relation between oxidative stress-related genes and CRC prognosis and their involvement in the immune microenvironment. Totally 101 OS-related genes were selected from the MsigDB database. Then, univariate Cox regression was used to explore the prognostic value of the selected genes correlated with the CRC patient survival in the TCGA database. A total of 9 prognostic OS-related genes in CRC were identified. Based on consensus clustering, CRC patients were then categorized into two molecular subtypes. A prognostic risk model containing 8 genes was established using Lasso regression, and CRC patients were divided into high or low-risk groups based on the median risk scores. The predictive value of the 8 genes in CRC prognosis was validated using ROC curves, which indicate that CTNNB1, STK25, RNF112, SFPQ, MMP3, and NOL3 were promising prognostic biomarkers in CRC. Furthermore, the immune cell infiltration levels in different risk groups or CRC subtypes were analyzed. We found that the high-risk or C1 subtype had immunosuppressive microenvironment, which might explain the unfavorable prognosis in the two groups of CRC patients. Additionally, functional experiments were conducted to investigate the effects of OS-related genes on CRC cell proliferation, stemness, and apoptosis. We found that CTNNB1, HSPB1, MMP3, and NOL3 were upregulated in CRC tissues and cells. Knockdown of CTNNB1, HSPB1, MMP3, and NOL3 significantly suppressed CRC cell proliferation, stemness and facilitated CRC cell apoptosis. In conclusion, we established prognostic CRC subtypes and an eight-gene risk model, which may provide novel prognostic indicators and benefit the design of individualized therapeutic strategies for CRC patients.

Untethered shape-changing devices in the gastrointestinal tract.

INTRODUCTION: Advances in microfabrication, automation, and computer engineering seek to revolutionize small-scale devices and machines. Emerging trends in medicine point to smart devices that emulate the motility, biosensing abilities, and intelligence of cells and pathogens that inhabit the human body. Two important characteristics of smart medical devices are the capability to be deployed in small conduits, which necessitates being untethered, and the capacity to perform mechanized functions, which requires autonomous shape-changing. AREAS COVERED: We motivate the need for untethered shape-changing devices in the gastrointestinal tract for drug delivery, diagnosis, and targeted treatment. We survey existing structures and devices designed and utilized across length scales from the macro to the sub-millimeter. These devices range from triggerable pre-stressed thin film microgrippers and spring-loaded devices to shape-memory and differentially swelling structures. EXPERT OPINION: Recent studies demonstrate that when fully enabled, tether-free and shape-changing devices, especially at sub-mm scales, could significantly advance the diagnosis and treatment of GI diseases ranging from cancer and inflammatory bowel disease (IBD) to irritable bowel syndrome (IBS) by improving treatment efficacy, reducing costs, and increasing medication compliance. We discuss the challenges and possibilities associated with ensuring safe, reliable, and autonomous operation of these smart devices.

Protective effects of maternal administration of total saponins of Codonopsis pilosula in the mice offspring following diarrhea: role of immune function, antioxidant function, and intestinal inflammatory injury.

Total saponins of Codonopsis (TSC) are a kind of critical bioactive substances in Codonopsis, which have anti-inflammatory, antioxidant, anti-ulcer, immunomodulatory effects, and protective effects on ulcerative enteritis. In this study, TSC (3.75 mL/kg, gavage) was administered once a day to 13-day gestation Kunming mice for 5 days. On day 13 of birth, the offspring were given Escherichia coli solution (0.15 mL/mouse, intraperitoneal injection) and senna leaf decoction (0.15 mL/mouse, gavage) once a day for 6 days. The results showed that gestation maternal administration of TSC effectively reduced the diarrhea index, increased the content of sIgA, IgG, SOD, and GSH, inhibited the TLR4/MyD88/NF-κB pathway in the intestine, reduced the expression of inflammatory factors, and alleviated intestinal injury in the littermates. The results provided a critical reference for the clinical application of TSC to control diarrhea in animal offspring.

An Activatable Near-Infrared Fluorescent Probe for Precise Detection of the Pulmonary Metastatic Tumors: A Traditional Molecule Having a Stunning Turn.

An accurate detection of lung metastasis is of great significance for making better treatment choices and improving cancer prognosis, but remains a big challenge in clinical practice. In this study, we propose a reinventing strategy to develop a pH-activatable near-infrared (NIR) fluorescent nanoprobe, pulmonary metastasis tracer (denoted as PMT), based on assembly of NIR dye IR780 and calcium phosphate (CaP). By delicately tuning the intermolecular interactions during the assembly process and dye doping content, as well as the synthetic condition of probe, the fluorescence of PMT could be finely adjusted via the tumor acidity-triggered disassembly. Notably, the selected PMT9 could sharply convert subtle pH variations into a distinct fluorescence signal to generate high fluorescence ON/OFF contrast, dramatically reducing the background signals. Benefiting from such preferable features, PMT9 is able to precisely identify not only the tumor sites in orthotopic lung cancer models but also the pulmonary metastases in mice with remarkable signal-to-background ratio (SBR). This study provides a unique strategy to turn shortcomings of traditional dye IR780 during in vivo imaging into advantages and further expand the application of fluorescent probe to image lung associated tumor lesions.

Dendritic Cell-Derived Exosomes Stimulated by Treponema pallidum Induce Endothelial Cell Inflammatory Response through the TLR4/MyD88/NF-κB Signaling Pathway.

Exosomes have been implicated in vascular damage in recent research. The influence of dendritic cell-derived exosomes generated by Treponema pallidum (T. pallidum) on the inflammatory process of vascular cells was examined in this study. Human umbilical vein endothelial cells (HUVECs) were cocultured with exosomes isolated from dendritic cells induced by T. pallidum. Western blot and reverse transcription-quantitative real-time polymerase chain reaction were used to assess toll-like receptor 4 (TLR4) expression and the quantity of proinflammatory cytokines. The findings showed that the expression of TLR4 was considerably upregulated, and TLR4 knockdown dramatically reduced interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production in exosome-treated HUVECs. Furthermore, TLR4 silencing reduced myeloid differentiation primary response protein 88 (MyD88) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) levels in exosome-treated HUVECs. Additionally, suppression of the activity of NF-κB with BAY11-7082, an NF-κB inhibitor, also reduced the exosome-treated inflammatory response. Our results suggested that dendritic cell-derived exosomes stimulated by T. pallidum induced endothelial cell inflammation, and the TLR4/MyD88/NF-κB signal axis was activated, significantly increasing IL-1ß, IL-6, and TNF-α expression. This may have a significant role in the vascular inflammatory response in syphilis, which would contribute to the understanding of the pathogenesis of syphilis and the host immunological response to T. pallidum.

Iron-based metal-organic framework co-loaded with buthionine sulfoximine and oxaliplatin for enhanced cancer chemo-ferrotherapy via sustainable glutathione elimination.

BACKGROUND: Emerging ferroptosis-driven therapies based on nanotechnology function either by increasing intracellular iron level or suppressing glutathione peroxidase 4 (GPX4) activity. Nevertheless, the therapeutic strategy of simultaneous iron delivery and GPX4 inhibition remains challenging and has significant scope for improvement. Moreover, current nanomedicine studies mainly use disulfide-thiol exchange to deplete glutathione (GSH) for GPX4 inactivation, which is unsatisfactory because of the compensatory effect of continuous GSH synthesis. METHODS: In this study, we design a two-in-one ferroptosis-inducing nanoplatform using iron-based metal-organic framework (MOF) that combines iron supply and GPX4 deactivation by loading the small molecule buthionine sulfoxide amine (BSO) to block de novo GSH biosynthesis, which can achieve sustainable GSH elimination and dual ferroptosis amplification. A coated lipid bilayer (L) can increase the stability of the nanoparticles and a modified tumor-homing peptide comprising arginine-glycine-aspartic acid (RGD/R) can achieve tumor-specific therapies. Moreover, as a decrease in GSH can alleviate resistance of cancer cells to chemotherapy drugs, oxaliplatin (OXA) was also loaded to obtain BSO&OXA@MOF-LR for enhanced cancer chemo-ferrotherapy in vivo. RESULTS: BSO&OXA@MOF-LR shows a robust tumor suppression effect and significantly improved the survival rate in 4T1 tumor xenograft mice, indicating a combined effect of dual amplified ferroptosis and GSH elimination sensitized apoptosis. CONCLUSION: BSO&OXA@MOF-LR is proven to be an efficient ferroptosis/apoptosis hybrid anti-cancer agent. This study is of great significance for the clinical development of novel drugs based on ferroptosis and apoptosis for enhanced cancer chemo-ferrotherapy.

Evaluation of between-assay consistency among laboratory testing methods for neurosyphilis: a systematic review.

We conducted a systematic review to analyse the consistency of nontreponemal-specific tests of Treponema pallidum in cerebrospinal fluid. We searched the PubMed, EMBASE, Web of Science, CNKI, Wanfang and Chongqing VIP databases. The inclusion criteria were studies conducted on nontreponemal-specific tests in cerebrospinal fluid (CSF) within the same population. Exclusion criteria were studies with incomplete data or where we were unable to obtain the full text, duplicate reports, case reports and studies without sensitivity or specificity results. We used kappa value analysis and McNemar's test to analyse study consistency. We initially collected a total of 198 articles and ultimately included six articles that involved 429 patients with neurosyphilis. The performance between venereal disease research laboratory tests (VDRL) and the reactive plasma regain or toluidine red serum unheated test was similar. The kappa value for consistency between VDRL and reactive plasma regain was >0.8 in three articles, and was 0.892 for consistency between VDRL and toluidine red serum unheated test in one article. Our results suggested that CSF-reactive plasma regain or CSF-toluidine red serum unheated test may serve as alternative tests in the diagnosis of neurosyphilis with CSF-VDRL.

Efficacy of robot-assisted vs. laparoscopy surgery in the treatment of colorectal cancer: A systematic review and meta-analysis.

PURPOSE: To compare the efficacy of robot-assisted colorectal surgery (RACS) vs. laparoscopic-assisted colorectal surgery (LACS) in the treatment of colorectal cancer (CRC). METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) reporting on RACS and LACS in CRC patients published up to January 4, 2022. The outcomes included operative time, length of stay, conversion, circumferential resection margin positivity (CRM+), and complications. RESULTS: Six RCTs (412 participants with RACS and 420 with LACS) were included. The pooled results showed shorter operative time (WMD=44.28, 95%CI: 9.36, 79.19, P = 0.013; PQ<0.001) and lower costs in RACS than in LACS (WMD=1546.15, 95%CI: 761.51, 2330.78, P<0.001; PQ=0.208), while no differences were observed for the length of stay (WMD=-0.31, 95%CI: -1.13,0.51, P = 0.456; I2=0.0%, PQ=0.990), blood loss (WMD=-33.72, 95%CI: -205.06, 137.62, P = 0.700; I2=89.0%, PQ=0.003), the number of harvested lymph nodes (WMD=1.38, 95%CI: -0.09, 2.85, P = 0.066; I2=0.0%, PQ=0.645), the time of first flatus (WMD=0.20, 95%CI: -0.20, 0.61, P = 0.328; I2=0.0%, PQ=0.337), rates of conversion to open surgery (RR=0.62, 95%CI: 0.38,1.01, P = 0.053; I2=0.0%, PQ=0.459), complication rates (RR=1.11, 95%CI: 0.83,1.49, P = 0.466; I2=0.0%, PQ=0.948), and CRM+ rates (RR=1.02, 95%CI: 0.66,1.58, P = 0.938; I2=0.0%, PQ=0.408). No publication bias was detected. The sensitivity analyses showed that the results for the operative time were robust. CONCLUSIONS: Patients with CRC who underwent RACS and LACS had a similar length of stay, blood loss, the time of first flatus, rates of conversion to open surgery, the number of harvested lymph nodes, complication rates, and CRM+ rates; however, RACS led to longer surgeries and higher costs than LACS.

Balance between pallidal neural oscillations correlated with dystonic activity and severity.

BACKGROUND AND OBJECTIVE: The balance between neural oscillations provides valuable insights into the organisation of neural oscillations related to brain states, which may play important roles in dystonia. We aim to investigate the relationship of the balance in the globus pallidus internus (GPi) with the dystonic severity under different muscular contraction conditions. METHODS: Twenty-one patients with dystonia were recruited. All of them underwent bilateral GPi implantation, and local field potentials (LFPs) from the GPi were recorded via simultaneous surface electromyography. The power spectral ratio between neural oscillations was computed as the measure of neural balance. This ratio was calculated under high and low dystonic muscular contraction conditions, and its correlation with the dystonic severity was assessed using clinical scores. RESULTS: The power spectral of the pallidal LFPs peaked in the theta and alpha bands. Within participant comparison showed that the power spectral of the theta oscillations significantly increased during high muscle contraction compared with that during low contraction. The power spectral ratios between the theta and alpha, theta and low beta, and theta and high gamma oscillations were significantly higher during high contraction than during low contraction. The total score and motor score were associated with the power spectral ratio between the low and high beta oscillations, which was correlated with the dystonic severity both during high and low contractions. The power spectral ratios between the low beta and low gamma and between the low beta and high gamma oscillations showed a significantly positive correlation with the total score during both high and low contractions; a correlation with the motor scale score was found only during high contraction. Meanwhile, the power spectral ratio between the theta and alpha oscillations during low contraction showed a significantly negative correlation with the total score. The power spectral ratios between the alpha and high beta, alpha and low gamma, and alpha and high gamma oscillations were significantly correlated with the dystonic severity only during low contraction. CONCLUSION: The balance between neural oscillations, as quantified by the power ratio between specific frequency bands, differed between the high and low muscular contraction conditions and was correlated with the dystonic severity. The balance between the low and high beta oscillations was correlated with the dystonic severity during both conditions, making this parameter a new possible biomarker for closed-loop deep brain stimulation in patients with dystonia.

Mesenchymal Stem Cell-Derived Exosomes are Effective for Radiation Enteritis and Essential for the Proliferation and Differentiation of Lgr5+ Intestinal Epithelial Stem Cells by Regulating Mir-195/Akt/ß-Catenin Pathway.

BACKGROUND: Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive. METHODS: In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5+ IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-α and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5+ IESC was tested. RESULTS: We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5+ IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/ß-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation. CONCLUSION: MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5+ IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt ß-catenin pathways.

Di (2-ethyl) hexyl phthalate induces liver injury in chickens by regulating PTEN/PI3K/AKT signaling pathway via reactive oxygen species.

Di (2-ethyl) hexyl phthalate (DEHP) is a common environmental endocrine disruptor that induces oxidative stress, posing a significant threat to human and animal health. Oxidative stress can activate the PTEN/PI3K/AKT pathway, which is closely related to cell apoptosis. However, it is unclear whether DEHP induces apoptosis of chicken liver cells by regulating the PTEN/PI3K/AKT pathway through oxidative stress. In this experiment, male laying hens were continuously exposed to 400 mg/kg, 800 mg/kg, and 1600 mg/kg DEHP for 14 d, 28 d, and 42 d. The results showed that liver injury was aggravated with the dose of DEHP gavage, and the ROS/MDA levels in L, M, and H DEHP exposure groups were significantly increased, while the T-AOC/T-SOD/GSH-PX levels were decreased. Meanwhile, DEHP exposure up-regulated the mRNA and protein expression levels of PTEN/Bax/Caspase-9/Caspase-3 and down-regulated the mRNA and protein expression levels of PI3K/AKT/BCL-2, indicating that DEHP may lead to hepatocyte apoptosis through ROS regulation of PTEN/PI3K/AKT axis. In order to further clarify the relationship between oxidative stress and liver injury, we treated chicken hepatocellular carcinoma cell line (LMH) with 2.5 mM N-acetylcysteine (NAC). NAC attenuated these phenomena. In summary, our study suggests that DEHP can induce apoptosis of chicken liver through ROS activation of the PTEN/PI3K/AKT axis.

Plasma Exosome-Derived microRNAs Profiles in Patients with Serofast Status: A Cross-Sectional Study.

Purpose: Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum (T. pallidum), which can lead to chronic morbidity and adverse complications. In clinical practice, serofast status (SF) patients present with clinical symptoms that are very similar to those of healthy individuals or syphilis-cured patients, and often require prolonged follow-up for diagnosis. Currently, there is increasing interest in the potential of plasma exosome-derived miRNA as a biomarker for the detection of infectious diseases. In this study, we aimed to explore the diagnostic potential of miRNA in SF and its possible biological implications. Patients and Methods: Exosome-derived miRNAs were isolated from peripheral plasma samples obtained from 20 patients with secondary syphilis (SS), SF, serologically cured syphilis (SC), and healthy controls (HC), and differentially expressed miRNAs (DEmiRNAs) were identified by microarray analysis. Prediction of potential target genes, functional annotation, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were then performed. The expression of selected miRNAs was confirmed in 37 patients by quantitative reverse transcription polymerase chain reaction (RT-qPCR). A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of these miRNAs in differentiating syphilis from HC or SC. Results: The expression profile of plasma exosome-derived miRNA was discovered in individuals with SF through microarray analysis. The targeted genes of DEmiRNAs were found to be involved in diverse biological processes according to GO and KEGG analysis, such as regulation of transcription, mitochondria, Golgi, immune system, apoptosis, Ras signaling pathway, etc. Using RT-qPCR validation, miR-1273g-3p, miR-4485-5p, miR-197-3p, and miR-1908-3p showed significant upregulation in patients with SF. These miRNAs exhibited a superior diagnostic ability, either individually or combined, to distinguish SF from SC or HC. Conclusion: The DEmiRNAs in plasma exosomes may play a role in the pathogenesis of SF and have the potential to become a noble and effective diagnostic method.

Sonodynamic-immunomodulatory nanostimulators activate pyroptosis and remodel tumor microenvironment for enhanced tumor immunotherapy.

Rationale: Spatiotemporal control of pyroptosis has a profound impact on cancer immunotherapy. Owing to the precise spatiotemporal control and reduction in the side effects of ultrasound (US), sonodynamic therapy (SDT) is expected to be a promising mean to activate pyroptosis. Furthermore, the pyroptosis-initiated immune response can be amplified by enhanced lymphocyte infiltration occurring due to extracellular matrix (ECM) depletion. Therefore, it is highly desirable to develop a sonodynamic-immunomodulatory strategy to amplify pyroptosis-mediated tumor immunotherapy by remodeling of the tumor microenvironment, thereby enhancing tumor immunotherapy. Methods: We reported a potent strategy based on a sonosensitizer, which is composed of LY364947-loaded porous coordination network (PCN-224) camouflaged with a red blood cell (RBC) membrane and evaluated pyroptosis activation, collagen depletion, immunocyte infiltration, and adaptive immune response during the pyroptosis-initiated immune response in vitro and in vivo. Results: The sonosensitizer generated reactive oxygen species (ROS) under US irradiation and initiated the caspase-3 apoptotic signaling pathway, which is regarded as the key upstream activator of gasdermin E (GSDME)-mediated pyroptosis. During the subsequent anti-tumor immune response mediated by pyroptosis, LY364947 loosened the ECM structure via collagen depletion, resulting in enhanced T-lymphocyte infiltration and nearly complete eradication of tumors in a mouse model with the formation of immunological memory. Conclusion: Our findings indicate that sonodynamic-immunomodulatory pyroptotic strategy exhibits robust anti-tumor immune efficacy as well as provides novel insights into the role of pyroptosis in cancer immunology.

Genome-wide identification and characterization of tomato 14-3-3 (SlTFT) genes and functional analysis of SlTFT6 under heat stress.

The plant 14-3-3 proteins are essential for many biological processes and responses to abiotic stress. We performed genome-wide identification and analysis of the 14-3-3 family genes in tomato. To explore the properties of the thirteen Sl14-3-3 found in the tomato genome, their chromosomal location, phylogenetic, and syntenic relationships were analyzed. The Sl14-3-3 promoters were found to have a number of growth-, hormone-, and stress-responsive cis-regulatory elements. Moreover, the qRT-PCR assay revealed that Sl14-3-3 genes are responsive to heat and osmotic stress. Subcellular localization experiments evidenced that the SlTFT3/6/10 proteins occur in the nucleus and cytoplasm Additional analysis on Sl14-3-3 putative interactor proteins revealed a number of prospective clients that potentially participate in stress reactions and developmental processes. Furthermore, overexpression of an Sl14-3-3 family gene, SlTFT6, improved tomato plants thermotolerance. Taken together, the study provides basic information on tomato 14-3-3 family genes in plant growth and abiotic stress response (high temperature stress), which can be helpful to further study the underlying molecular mechanisms.

An Integrative Model of In-Hospital and Out-of-Hospital Nursing Care for Non-Suicidal Self-Injury: A Narrative Review.

BACKGROUND: Non-suicidal self-injury (NSSI) refers to the intentional and repeated physical trauma of an individual without explicit suicidal intent, which has negative effects on the physical and mental well-being of an individual, especially for adolescents. Timely and accessible nursing care may play an important role in the survival and rehabilitation process of NSSI. METHODS: In this review, we systematically discuss the nursing care of NSSI behavior and provide recommendations based on an integrated nursing model for NSSI management. RESULTS: As reported in previous studies, a variety of factors can contribute to NSSI behavior, such as personality traits, current psychological status, history of mental illnesses, as well as family and social factors. In-hospital care is the most necessary and effective care during acute episodes of NSSI behavior. To effectively manage inpatients with NSSI behaviors, nurses should first understand the motivation of NSSI, and provide comprehensive and multi-level care through nurse-patient communication, individualized psychological care, and multidisciplinary cooperation with other professionals. While the purpose of out-of-hospital nursing is to reduce the frequency of NSSI behaviors by screening high-risk individuals, providing psychological support, promoting health education, and improving self-awareness. CONCLUSIONS: An integrative model of in-hospital and out-of-hospital nursing care can help improve the clinical management and long-term prognosis of patients with NSSI and minimize the risk of suicidal ideation or suicidal behavior.

Identification of potential immune-related ceRNA Regulatory Network in UVB-irradiated human skin.

For a better understanding the molecular biomarkers in UVB-induced skin damage, and its potential mechanism, we downloaded two microarray data sets on skin UVB damage from the Gene Expression Omnibus (GEO): GSE21429, GSE56754. By using the Limma package to analyze differential gene expression and co-expression network analysis to screen module genes, 16 common genes were identified (16 up-regulated). Gene Ontology analysis to explore the functional roles of these genes indicated that the common genes were associated mainly with melanin biosynthetic process and metabolic process. Gene Set Enrichment Analysis provided evidence that the most gene sets enriched in immune and inflammation-related signaling pathways in the UVB-treated subjects, as compared with the untreated subjects. The PPI network genes were ranked according to the degree of connectivity, the top three ranked genes: "MLANA", "GPR143" and "SFTPC" were identified as potential biomarkers using the area under the receiver operating characteristic curve. The relative proportion of 22 immune cell types was then calculated by using the CIBERSORT algorithm. A higher follicular helper T cell ratio in UVB-treated samples compared to untreated samples was observed. Moreover, three hub genes have also been shown to be associated with immune cells. Finally, through multiple online miRNA databases, we propose MLANA-miR-573-MALAT1/NEAT1, GPR143-miR-138-5p-MALAT1/ KCNQ1OT1 might be potential RNA regulatory pathways that control disease progression in UVB-induced skin damage. In summary, the present results provide novel insights into the UVB-radiation related biological process changes, and further offer a new clinical application for prognosis and diagnostic prediction of UVB radiation-mediated skin damage.