Disturbed glycolipid metabolism activates CXCL13-CXCR5 axis in senescent TSCs to promote heterotopic ossification.

Heterotopic ossification (HO) occurs as a common complication after injury, while its risk factor and mechanism remain unclear, which restricts the development of pharmacological treatment. Clinical research suggests that diabetes mellitus (DM) patients are prone to developing HO in the tendon, but solid evidence and mechanical research are still needed. Here, we combined the clinical samples and the DM mice model to identify that disordered glycolipid metabolism aggravates the senescence of tendon-derived stem cells (TSCs) and promotes osteogenic differentiation. Then, combining the RNA-seq results of the aging tendon, we detected the abnormally activated autocrine CXCL13-CXCR5 axis in TSCs cultured in a high fat, high glucose (HFHG) environment and also in the aged tendon. Genetic inhibition of CXCL13 successfully alleviated HO formation in DM mice, providing a potential therapeutic target for suppressing HO formation in DM patients after trauma or surgery.

Hnrnpk protects against osteoarthritis through targeting WWC1 mRNA and inhibiting Hippo signaling pathway.

Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.

Occult urothelial carcinoma with mediastinal metastasis: A case report.

Occult urothelial carcinoma (UC), particularly with mediastinal metastases, is an uncommon clinical occurrence. The present study describes the unusual case of a 70-year-old male patient who developed mediastinal metastases from an occult UC. Histological evaluations and immunohistochemical features of the mediastinal tumor were indicative of UC; however, extensive imaging failed to identify the primary urological lesion. The findings suggest that mediastinal metastases from UCs, despite their rarity, should be considered in cases where patients with mediastinal tumors exhibit chest-related symptoms. Prompt pathological examinations are crucial for ascertaining the nature and origin of the tumor. Moreover, individualized treatment should be performed in strict accordance with the established oncology guidelines.

Research progress on the correlation between platelet aggregation and tumor progression.

Platelets are generally considered as the main functional unit of the coagulation system. However, more and more studies have confirmed that platelets also have an important relationship with tumor progression. Tumor cells can utilize platelets to promote their own infiltration and hematogenous metastasis, and platelets are activated and aggregated in this process. Therefore, platelet aggregation may be a concomitant marker of tumor progression. This is of great significance for predicting tumor metastasis before timely treatments.

Pyroptosis in microbial infectious diseases.

Pyroptosis is a gasdermins-mediated programmed cell death that plays an essential role in immune regulation, and its role in autoimmune disease and cancer has been studied extensively. Increasing evidence shows that various microbial infections can lead to pyroptosis, associated with the occurrence and development of microbial infectious diseases. This study reviews the recent advances in pyroptosis in microbial infection, including bacterial, viral, and fungal infections. We also explore potential therapeutic strategies for treating microbial infection-related diseases by targeting pyroptosis.

The effectiveness of fracture liaison services in patients with hip fractures: A systematic review and meta-analysis of randomized controlled trials.

Background: In recent years, fracture liaison services (FLS) have been applied for hip fractures; however, their effectiveness remains uncertain. Objective: To evaluate the effectiveness of FLS in patients with hip fractures. Design: A systematic review and meta-analysis of randomized controlled trials. Data sources: Embase, PubMed, Cochrane Library, Ebsco, Ovid, Web of Science, Medline, CNKI, Wangfang, and Vip were searched from their date of inception to March 2023. Two researchers screened the literature based on the inclusion and exclusion criteria, evaluated the quality, extracted data, and conducted a meta-analysis using ReviewManager 5.4. Results: After screening, 12 randomised controlled trials (RCT) including 2136 patients were used in the meta-analysis. The primary outcomes were hip function rate of recurrent fracture, medication adherence, and degree of weakness. FLS improved hip function in patients with hip fractures [MD = 9.37, 95 % CI (7.69, 11.06), P < 0.0001], P < 0.0001], medication adherence [OR = 10.59, 95 % CI (1.64, 68.41), P＜0.0001], degree of weakness [MD = -1.45, 95%CI (-1.68，-1.23), P＜0.0001], and reduced the rate of recurrent fractures [OR = 0.60, 95 % CI (0.44, 0.82). Conclusion: Implementation of the FLS management model was beneficial for patients with hip fractures. It can positively impact the prognosis of patients with hip fractures by improving hip function, reducing the rate of recurrent fractures, and improving medication adherence and degree of weakness.

Case Report: Ensartinib for gastric epithelioid inflammatory myofibrosarcoma with STRN-ALK fusion.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a highly aggressive malignant subtype of inflammatory myofibroblastoma (IMT) associated with poor prognosis. IMT can occur in various parts of the body, most frequently in the lungs, followed by the mesentery, omentum, retroperitoneum, and pelvis, among other areas; however, it is exceptionally rare in the stomach. Anaplastic lymphoma kinase (ALK) is a critical driver of lung cancer development and is currently the "gold standard" target for non-small cell lung cancer treatment. However, there are few reports on the use of ALK inhibitors for EIMS, necessitating further investigation. A male patient with postoperative inflammatory myofibroblastic sarcoma of the stomach received postoperative chemotherapy and had a stable outcome. However, a repeat CT scan performed 11 months later revealed disease progression. The patient later underwent immunohistochemistry testing that indicated ALK positivity, and next-generation sequencing revealed STRN-ALK fusion. Ensartinib 225 mg qd was administered as recommended, and the patient experienced only mild pruritus and no adverse effects such as rash. Eight months after CT follow-up, the patient's subseptal soft tissue nodules had decreased, and the outcome was assessed as a partial response. The findings of this case report introduce a novel strategy for treating ALK-positive EIMS that utilizes ensartinib, a drug with previously demonstrated success in the treatment of ALK-positive cancer.

Improving the Herbicide Resistance of Rice 4-Hydroxyphenylpyruvate Dioxygenase by DNA Shuffling Basis-Directed Evolution.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an ideal target for herbicide resistance genetic engineering. In this study, a mutant MFRR-2 with mesotrione resistance was screened from an Oryza sativa HPPD and mutant-Zea mays HPPD DNA shuffling library. The enzyme properties showed that although the stability of the mutant decreased in vitro, the enzyme activity of MFRR-2 at the optimum temperature of 25 °C was still equivalent to that of OsHPPD. Under 50 µM mesotrione treatment, MFRR-2 enzyme activity remained at approximately 90%, while the enzyme activity of OsHPPD decreased by approximately 50%. Surprisingly, Fe2+ was found to have an inhibitory effect on the enzyme activity. Then, the transgenic rice of the MFRR-2 gene showed approximately 1.5 times mesotrione resistance compared to OsHPPD transgenic rice. In conclusion, this study has conducted a beneficial exploration on the use of DNA shuffling for HPPD-directed evolution, and the mutant has potential application value for herbicide resistance genetic engineering.

MiR-184 targeting FOXO1 regulates host-cell oxidative stress induced by Chlamydia psittaci via the Wnt/ß-catenin signaling pathway.

Chlamydia psittaci is a human pathogen that causes atypical pneumonia after zoonotic transmission. We confirmed that C. psittaci infection induces oxidative stress in human bronchial epithelial (HBEs) cells and explored how this is regulated through miR-184 and the Wnt/ß-catenin signaling pathway. miR-184 mimic, miR-184 inhibitor, FOXO1 siRNA, or negative control sequence was transfected into HBE cells cultured in serum-free medium using Lipofectamine 2000. Then, prior to the cells were infected with C. psittaci 6BC, and the cells were treated with or without 30 µM Wnt/ß-catenin inhibitor ICG-001. Quantification of reactive oxygen species, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione was carried out according to the manufacturer's protocol using a corresponding assay kit. The outcome of both protein and gene was measured by western blotting or real-time fluorescence quantitative PCR. In C. psittaci-infected HBE cells, miR-184 was upregulated, while one of its target genes, FOXO1, was downregulated. ROS and MDA levels increased, while SOD and GSH contents decreased after C. psittaci infection. When miR-184 expression was downregulated, the level of oxidative stress caused by C. psittaci infection was reduced, and the Wnt/ß-catenin signaling pathway was inhibited. The opposite results were seen when miR-184 mimic was used. Transfecting with FOXO1 siRNA reversed the effect of miR-184 inhibitor. Moreover, when the Wnt/ß-catenin-specific inhibitor ICG-001 was used, the level of oxidative stress induced by C. psittaci infection was significantly suppressed. miR-184 can target FOXO1 to promote oxidative stress in HBE cells following C. psittaci infection by activation of the Wnt/ß-catenin signaling pathway.

An Intelligent Water Monitoring IoT System for Ecological Environment and Smart Cities.

Global precipitation is becoming increasingly intense due to the extreme climate. Therefore, creating new technology to manage water resources is crucial. To create a sustainable urban and ecological environment, a water level and water quality control system implementing artificial intelligence is presented in this research. The proposed smart monitoring system consists of four sensors (two different liquid level sensors, a turbidity and pH sensor, and a water oxygen sensor), a control module (an MCU, a motor, a pump, and a drain), and a power and communication system (a solar panel, a battery, and a wireless communication module). The system focuses on low-cost Internet of Things (IoT) devices along with low power consumption and high precision. This proposal collects rainfall from the preceding 10 years in the application region as well as the region's meteorological bureau's weekly weather report and uses artificial intelligence to compute the appropriate water level. More importantly, the adoption of dynamic adjustment systems can reserve and modify water resources in the application region more efficiently. Compared to existing technologies, the measurement approach utilized in this study not only achieves cost savings exceeding 60% but also enhances water level measurement accuracy by over 15% through the successful implementation of water level calibration decisions utilizing multiple distinct sensors. Of greater significance, the dynamic adjustment systems proposed in this research offer the potential for conserving water resources by more than 15% in an effective manner. As a result, the adoption of this technology may efficiently reserve and distribute water resources for smart cities as well as reduce substantial losses caused by anomalous water resources, such as floods, droughts, and ecological concerns.

Rubiadin-1-methyl ether inhibits BECN1 transcription and Beclin1-dependent autophagy during osteoclastogenesis by inhibiting NF-κB p65 activation.

As an active substance isolated from the root of Morinda officinalis How., rubiadin-1-methyl ether (RBM), can improve osteoporosis due to its inhibition on osteoclastogenesis. Autophagy plays a key role in osteoclastogenesis. Our research aims to explore the relationship between RBM, autophagy, and osteoclastogenesis. Our results showed that RBM not only inhibited the differentiation level of osteoclasts and the proliferation ability of osteoclast precursors (OCPs), but also repressed the autophagic activity in OCPs (LC3 transformation and the number of autophagosomes observed by transmission electron microscopy). However, RBM-inhibited osteoclast differentiation and OCP autophagy (LC3 transformation and LC3-puncta formation) could be reversed by the application of TAT-Beclin1. Moreover, RBM administration reduced RANKL-induced p65 phosphorylation and p65 nuclear translocation in OCPs. In addition, the addition of RBM inhibited Beclin1 protein level and BECN1 (the gene form of Beclin1) mRNA level in OCPs increased by RANKL. Importantly, the reduction in the expression of BECN1 and Beclin1, LC3 transformation, and osteoclastic differentiation in OCPs caused by RBM were reversed by p65 overexpression. In conclusion, RBM may reduce the transcription of BECN1 by inhibiting the activation of nuclear factor kappa B (NF-κB) p65, thereby inhibiting Beclin1-dependent autophagy and RANKL-induced osteoclastogenesis.

Current Status and Future Trends of Cold Atmospheric Plasma as an Oncotherapy.

Cold atmospheric plasma (CAP), a redox modulation tool, is capable of inhibiting a wide spectrum of cancers and has thus been proposed as an emerging onco-therapy. However, with incremental successes consecutively reported on the anticancer efficacy of CAP, no consensus has been made on the types of tumours sensitive to CAP due to the different intrinsic characteristics of the cells and the heterogeneous design of CAP devices and their parameter configurations. These factors have substantially hindered the clinical use of CAP as an oncotherapy. It is thus imperative to clarify the tumour types responsive to CAP, the experimental models available for CAP-associated investigations, CAP administration strategies and the mechanisms by which CAP exerts its anticancer effects with the aim of identifying important yet less studied areas to accelerate the process of translating CAP into clinical use and fostering the field of plasma oncology.

Hnrnpk is essential for embryonic limb bud development as a transcription activator and a collaborator of insulator protein Ctcf.

Proper development of the limb bud relies on the concordance of various signals, but its molecular mechanisms have not yet been fully illustrated. Here we report that heterogeneous nuclear ribonucleoprotein K (hnRNPK) is essential for limb bud development. Its ablation in the limb bud results in limbless forelimbs and severe deformities of the hindlimbs. In terms of mechanism, hnRNPK functions as a transcription activator for the vital genes involved in the three regulatory axes of limb bud development. Simultaneously, for the first time we elucidate that hnRNPK binds to and coordinates with the insulator protein CCCTC binding factor (CTCF) to maintain a three-dimensional chromatin architecture. Ablation of hnRNPK weakens the binding strength of CTCF to topologically associating domain (TAD) boundaries, then leading to the loose TADs, and decreased interactions between promoters and enhancers, and further decreased transcription of developmental genes. Our study establishes a fundamental and novel role of hnRNPK in regulating limb bud development.

Metabolic reprogramming and epigenetic modifications in cancer: from the impacts and mechanisms to the treatment potential.

Metabolic reprogramming and epigenetic modifications are hallmarks of cancer cells. In cancer cells, metabolic pathway activity varies during tumorigenesis and cancer progression, indicating regulated metabolic plasticity. Metabolic changes are often closely related to epigenetic changes, such as alterations in the expression or activity of epigenetically modified enzymes, which may exert a direct or an indirect influence on cellular metabolism. Therefore, exploring the mechanisms underlying epigenetic modifications regulating the reprogramming of tumor cell metabolism is important for further understanding tumor pathogenesis. Here, we mainly focus on the latest studies on epigenetic modifications related to cancer cell metabolism regulations, including changes in glucose, lipid and amino acid metabolism in the cancer context, and then emphasize the mechanisms related to tumor cell epigenetic modifications. Specifically, we discuss the role played by DNA methylation, chromatin remodeling, noncoding RNAs and histone lactylation in tumor growth and progression. Finally, we summarize the prospects of potential cancer therapeutic strategies based on metabolic reprogramming and epigenetic changes in tumor cells.

Cellular membrane-targeting ruthenium complexes as efficient photosensitizers for broad-spectrum antibacterial activity.

A ruthenium complex [Ru(phen)2(phen-5-amine)-C14] (Ru-C14) with broad-spectrum antibacterial activity was designed and synthesized; positively charged Ru-C14 could target bacteria via electrostatic interactions and showed high binding effectiveness to cell membranes. In addition, Ru-C14 could act as a photosensitizer. Under 465 nm light irradiation, Ru-C14 could generate 1O2, thus disrupting the bacterial intracellular redox balance and leading to bacterial death. Ru-C14 also exhibited minimum inhibitory concentration values of 6.25 µM against Escherichia coli and 3.125 µM against Staphylococcus aureus; these values are lower than those of streptomycin and methicillin. This work combined the merits of cell membrane targeting and photodynamic therapy for antibacterial activity. The findings might open up a new avenue for effective anti-infection treatment and other medical applications.

Spatiotemporal Characterization of Human Early Intervertebral Disc Formation at Single-Cell Resolution.

The intervertebral disc (IVD) acts as a fibrocartilaginous joint to anchor adjacent vertebrae. Although several studies have demonstrated the cellular heterogeneity of adult mature IVDs, a single-cell transcriptomic atlas mapping early IVD formation is still lacking. Here, the authors generate a spatiotemporal and single cell-based transcriptomic atlas of human IVD formation at the embryonic stage and a comparative mouse transcript landscape. They identify two novel human notochord (NC)/nucleus pulposus (NP) clusters, SRY-box transcription factor 10 (SOX10)+ and cathepsin K (CTSK)+ , that are distributed in the early and late stages of IVD formation and they are validated by lineage tracing experiments in mice. Matrisome NC/NP clusters, T-box transcription factor T (TBXT)+ and CTSK+ , are responsible for the extracellular matrix homeostasis. The IVD atlas suggests that a subcluster of the vertebral chondrocyte subcluster might give rise to an inner annulus fibrosus of chondrogenic origin, while the fibroblastic outer annulus fibrosus preferentially expresseds transgelin and fibromodulin . Through analyzing intercellular crosstalk, the authors further find that notochordal secreted phosphoprotein 1 (SPP1) is a novel cue in the IVD microenvironment, and it is associated with IVD development and degeneration. In conclusion, the single-cell transcriptomic atlas will be leveraged to develop preventative and regenerative strategies for IVD degeneration.

Monitoring green tea fixation quality by intelligent sensors: comparison of image and spectral information.

BACKGROUND: Intelligent monitoring of fixation quality is a prerequisite for automated green tea processing. To meet the requirements of intelligent monitoring of fixation quality in large-scale production, fast and non-destructive detection means are urgently needed. Here, smartphone-coupled micro near-infrared spectroscopy and a self-built computer vision system were used to perform rapid detection of the fixation quality in green tea processing lines. RESULTS: Spectral and image information from green tea samples with different fixation degrees were collected at-line by two intelligent monitoring sensors. Competitive adaptive reweighted sampling and correlation analysis were employed to select feature variables from spectral and color information as the target data for modeling, respectively. The developed least squares support vector machine (LS-SVM) model by spectral information and the LS-SVM model by image information achieved the best discriminations of sample fixation degree, with both prediction set accuracies of 100%. Compared to the spectral information, the image information-based support vector regression model performed better in moisture prediction, with a correlation coefficient of prediction of 0.9884 and residual predictive deviation of 6.46. CONCLUSION: The present study provided a rapid and low-cost means of monitoring fixation quality, and also provided theoretical support and technical guidance for the automation of the green tea fixation process. © 2022 Society of Chemical Industry.

One-step synthesis of nitrogen-functionalized graphene aerogel for efficient removal of hexavalent chromium in water.

The efficient removal of hexavalent chromium (Cr(VI)) with high toxicity has attracted widespread concern since it causes serious harm to ecological environment and public health. Herein, we report a novel nitrogen-functionalized graphene aerogel with stereoscopic structure through a simple hydrothermal method and freeze drying for Cr(VI) removal from water. Graphene oxide (GO) and nitrogenous organics polyethyleneimine (PEI) and pyrrole are used as raw materials for preparing PEI/polypyrrole/GO aerogel (PPGA) adsorbent. PEI and pyrrole act as nitrogen sources to introduce nitrogenous functional groups, and also take on the role of cross-linkers for helping GO sheets to form stereoscopic structure. The obtained PPGA has a fast adsorption rate, excellent reusability, and shows a remarkable adsorption capacity for Cr(VI) up to 458.24 mg/g under the optimal conditions (pH 2.0, 298 K, Cr(VI): 600 mg/L, dosage: 0.4 g/L). The adsorption process of Cr(VI) on PPGA can fit the pseudo-second-order kinetic model well. Analysis of intraparticle diffusion shows that the Cr(VI) removal process is a multi-step process. Adsorption thermodynamic and isotherm results demonstrate Cr(VI) adsorption on PPGA is a spontaneous endothermic process. The adsorption mechanism involves electrostatic attraction, redox, and chelation. In general, this work provides a simple and eco-friendly way to prepare PPGA, which has a great potential for actual application of Cr(VI) removal in effluent.

Visualizing chemical indicators: Spatial and temporal quality formation and distribution during black tea fermentation.

Fermentation is a key black tea processing step and makes an important contribution to quality formation. Current approaches to fermentation monitoring are costly or laboratory-based. Here, we first evaluated the potential of at-line computer vision for detecting fermentation quality in a tea factory. A self-built industrial camera was used to collect tea samples at various fermentation durations. The correlations of color variables that were extracted from the images with key quality indicators in the tea samples were verified. Subsequently, partial least-squares regression models based on the color variables showed high prediction accuracy with residual prediction deviation values of 4.13, 3.53, and 3.39 for catechins, theaflavins and chlorophylls, respectively. Finally, the spatial and temporal distributions of indicators during fermentation were mapped to visualize the fermentation quality. This study realized low-cost, at-line and real-time detection for black tea fermentation, which provides technical support for the industrial and intelligent production of black tea.

Association of Disparities in Family History and Family Cancer History in the Electronic Health Record With Sex, Race, Hispanic or Latino Ethnicity, and Language Preference in 2 Large US Health Care Systems.

Importance: Clinical decision support (CDS) algorithms are increasingly being implemented in health care systems to identify patients for specialty care. However, systematic differences in missingness of electronic health record (EHR) data may lead to disparities in identification by CDS algorithms. Objective: To examine the availability and comprehensiveness of cancer family history information (FHI) in patients' EHRs by sex, race, Hispanic or Latino ethnicity, and language preference in 2 large health care systems in 2021. Design, Setting, and Participants: This retrospective EHR quality improvement study used EHR data from 2 health care systems: University of Utah Health (UHealth) and NYU Langone Health (NYULH). Participants included patients aged 25 to 60 years who had a primary care appointment in the previous 3 years. Data were collected or abstracted from the EHR from December 10, 2020, to October 31, 2021, and analyzed from June 15 to October 31, 2021. Exposures: Prior collection of cancer FHI in primary care settings. Main Outcomes and Measures: Availability was defined as having any FHI and any cancer FHI in the EHR and was examined at the patient level. Comprehensiveness was defined as whether a cancer family history observation in the EHR specified the type of cancer diagnosed in a family member, the relationship of the family member to the patient, and the age at onset for the family member and was examined at the observation level. Results: Among 144 484 patients in the UHealth system, 53.6% were women; 74.4% were non-Hispanic or non-Latino and 67.6% were White; and 83.0% had an English language preference. Among 377 621 patients in the NYULH system, 55.3% were women; 63.2% were non-Hispanic or non-Latino, and 55.3% were White; and 89.9% had an English language preference. Patients from historically medically undeserved groups-specifically, Black vs White patients (UHealth: 17.3% [95% CI, 16.1%-18.6%] vs 42.8% [95% CI, 42.5%-43.1%]; NYULH: 24.4% [95% CI, 24.0%-24.8%] vs 33.8% [95% CI, 33.6%-34.0%]), Hispanic or Latino vs non-Hispanic or non-Latino patients (UHealth: 27.2% [95% CI, 26.5%-27.8%] vs 40.2% [95% CI, 39.9%-40.5%]; NYULH: 24.4% [95% CI, 24.1%-24.7%] vs 31.6% [95% CI, 31.4%-31.8%]), Spanish-speaking vs English-speaking patients (UHealth: 18.4% [95% CI, 17.2%-19.1%] vs 40.0% [95% CI, 39.7%-40.3%]; NYULH: 15.1% [95% CI, 14.6%-15.6%] vs 31.1% [95% CI, 30.9%-31.2%), and men vs women (UHealth: 30.8% [95% CI, 30.4%-31.2%] vs 43.0% [95% CI, 42.6%-43.3%]; NYULH: 23.1% [95% CI, 22.9%-23.3%] vs 34.9% [95% CI, 34.7%-35.1%])-had significantly lower availability and comprehensiveness of cancer FHI (P < .001). Conclusions and Relevance: These findings suggest that systematic differences in the availability and comprehensiveness of FHI in the EHR may introduce informative presence bias as inputs to CDS algorithms. The observed differences may also exacerbate disparities for medically underserved groups. System-, clinician-, and patient-level efforts are needed to improve the collection of FHI.