Pristine/magnesium-loaded biochar and ZVI affect rice grain arsenic speciation and cadmium accumulation through different pathways in an alkaline paddy soil.

Cadmium (Cd) and arsenic (As) co-contamination has threatened rice production and food safety. It is challenging to mitigate Cd and As contamination in rice simultaneously due to their opposite geochemical behaviors. Mg-loaded biochar with outstanding adsorption capacity for As and Cd was used for the first time to remediate Cd/As contaminated paddy soils. In addition, the effect of zero-valent iron (ZVI) on grain As speciation accumulation in alkaline paddy soils was first investigated. The effect of rice straw biochar (SC), magnesium-loaded rice straw biochar (Mg/SC), and ZVI on concentrations of Cd and As speciation in soil porewater and their accumulation in rice tissues was investigated in a pot experiment. Addition of SC, Mg/SC and ZVI to soil reduced Cd concentrations in rice grain by 46.1%, 90.3% and 100%, and inorganic As (iAs) by 35.4%, 33.1% and 29.1%, respectively, and reduced Cd concentrations in porewater by 74.3%, 96.5% and 96.2%, respectively. Reductions of 51.6% and 87.7% in porewater iAs concentrations were observed with Mg/SC and ZVI amendments, but not with SC. Dimethylarsinic acid (DMA) concentrations in porewater and grain increased by a factor of 4.9 and 3.3, respectively, with ZVI amendment. The three amendments affected grain concentrations of iAs, DMA and Cd mainly by modulating their translocation within plant and the levels of As(III), silicon, dissolved organic carbon, iron or Cd in porewater. All three amendments (SC, Mg/SC and ZVI) have the potential to simultaneously mitigate Cd and iAs accumulation in rice grain, although the pathways are different.

[Study on the value of systemic immune inflammation index and nomogram in predicting the prognosis of patients with mucoepidermoid carcinoma].

PURPOSE: To investigate the relationship between preoperative systemic immune-inflammation index (SII) and relapse-free survival (RFS) after surgical resection of mucoepidermoid carcinoma(MEC). METHODS: The data of 135 patients with MEC who underwent surgical resection in the First Affiliated Hospital of Zhengzhou University from January 2016 to July 2019 were collected, and the receiver operating characteristic(ROC) curve was performed on the SII of patients. The optimal cut-off value was obtained by ROC analysis. Therefore, the patients' SII index was divided into high and low group, and survival analysis was performed by Kaplan-Meier method. Cox proportional regression model and least absolute shrinkage and selection operator (LASSO) were used to analyze the factors influencing prognosis, and a nomogram model was built to predict patients' relapse-free survival(RFS). Area under curve (AUC) and correction curve were used to evaluate the model and verify the consistency. RESULTS: Survival analysis showed that the RFS rate in low SII group was significantly higher than that in high SII group. Cox proportional hazard regression model showed high SII(HR=2.179, 95%CI: 1.072-4.426, P=0.031) and low tumor differentiation(HR=6.894, 95%CI: 2.770-17.158, P=0.000) and cervical lymph node metastasis (HR=2.091, 95%CI: 1.034-4.230, P=0.040) were significant predictors of poor RFS. CONCLUSIONS: The lower the preoperative SII, the better the prognosis of patients. The nomogram prognosis of MEC based on SII is effective.

Case report: PCA-2-associated encephalitis with different clinical phenotypes: a two-case series and literature review.

Purkinje cell cytoplasmic antibody type 2 (PCA-2), identified in 2000, targets the widely distributed microtubule-associated protein 1B in the central and peripheral nervous systems, leading to diverse clinical phenotypes of neurological disorders. We report two cases of PCA-2-associated encephalitis, each presenting with distinct onset forms and clinical manifestations, thereby illustrating the phenotypic variability of PCA-2-related diseases. The first patient was diagnosed with PCA-2-associated autoimmune cerebellitis and undifferentiated small cell carcinoma with metastasis in mediastinal lymph nodes of unknown primary origin. The second patient was diagnosed with PCA-2-associated limbic encephalitis. Our findings underscore the superior sensitivity of positron emission tomography-computed tomography over brain magnetic resonance imaging in the early detection of PCA-2-associated encephalitis. Given the high risk of relapse and suboptimal response to traditional immunotherapy in PCA-2-related neurological disorders, this study highlights the need for a deeper understanding of their pathogenesis to develop more effective treatments to control symptoms and improve patient prognosis.

Modulation of mercaptopurine intestinal toxicity and pharmacokinetics by gut microbiota.

The interaction between the gut microbiota and mercaptopurine (6-MP), a crucial drug used in pediatric acute lymphoblastic leukemia (ALL) treatment, has not been extensively studied. Here we reveal the significant perturbation of gut microbiota after 2-week 6-MP treatment in beagles and mice followed by the functional prediction that showed impairment of SCFAs production and altered amino acid synthesis. And the targeted metabolomics in plasma also showed changes in amino acids. Additionally, targeted metabolomics analysis of feces showed changes in amino acids and SCFAs. Furthermore, ablating the intestinal microbiota by broad-spectrum antibiotics exacerbated the imbalance of amino acids, particularly leading to a significant decrease in the concentration of S-adenosylmethionine (SAM). Importantly, the depletion of gut microbiota worsened the damage of small intestine caused by 6-MP, resulting in increased intestinal permeability. Considering the relationship between toxicity and 6-MP metabolites, we conducted a pharmacokinetic study in pseudo germ-free rats to confirm that gut microbiota depletion altered the methylation metabolites of 6-MP. Specifically, the concentration of MeTINs, a secondary methylation metabolite, showed a negative correlation with SAM, the pivotal methyl donor. Additionally, we observed a strong correlation between Alistipes and SAM levels in both feces and plasma. In conclusion, our study demonstrates that 6-MP disrupts the gut microbiota, and depleting the gut microbiota exacerbates 6-MP-induced intestinal toxicity. Moreover, SAM derived from microbiota plays a crucial role in influencing plasma SAM and the methylation of 6-MP. These findings underscore the importance of comprehending the role of the gut microbiota in 6-MP metabolism and toxicity.

A Universal Self-Propagating Synthesis of Aluminum-Based Oxyhalide Solid-State Electrolytes.

Inorganic solid-state electrolytes (SSEs) play a vital role in high-energy all-solid-state batteries (ASSBs). However, the current method of SSE preparation usually involves high-energy mechanical ball milling and/or a high-temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost-effective aluminum-based oxyhalide SSEs, which involves a self-propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum-based oxyhalide SSEs with tunable components and high ionic conductivities (over 10-3 S cm-1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum-based oxyhalide SSEs synthesized by our approach could further promote practical application of high-energy-density ASSBs.

Reverse water-gas shift catalyzed by RhnVO3,4- (n = 3-7) cluster anions under variable temperatures.

A fundamental understanding of the exact structural characteristics and reaction mechanisms of interface active sites is vital to engineering an energetic metal-support boundary in heterogeneous catalysis. Herein, benefiting from a newly developed high-temperature ion trap reactor, the reverse water-gas shift (RWGS) (CO2 + H2 → CO + H2O) catalyzed by a series of compositionally and structurally well-defined RhnVO3,4- (n = 3-7) clusters were identified under variable temperatures (298-773 K). It is discovered that the Rh5-7VO3,4- clusters can function more effectively to drive RWGS at relatively low temperatures. The experimentally observed size-dependent catalytic behavior was rationalized by quantum-chemical calculations; the framework of RhnVO3,4- is constructed by depositing the Rhn clusters on the VO3,4 "support", and a sandwiched base-acid-base [Rhout--Rhin+-VO3,4-; Rhout and Rhin represent the outer and inner Rh atoms, respectively] feature in Rh5-7VO3,4- governs the adsorption and activation of reactants as well as the facile desorption of the products. In contrast, isolated Rh5-7- clusters without the electronic modification of the VO3,4 "support" can only catalyze RWGS under relatively high-temperature conditions.

Selenium Nanomaterials Enhance the Nutrients and Functional Components of Fuding Dabai Tea.

Theanine, polyphenols, and caffeine not only affect the flavor of tea, but also play an important role in human health benefits. However, the specific regulatory mechanism of Se NMs on fat-reducing components is still unclear. In this study, the synthesis of fat-reducing components in Fuding Dabai (FDDB) tea was investigated. The results indicated that the 100-bud weight, theanine, EGCG, total catechin, and caffeine contents of tea buds were optimally promoted by 10 mg·L-1 Se NMs in the range of 24.3%, 36.2%, 53.9%, 67.1%, and 30.9%, respectively. Mechanically, Se NMs promoted photosynthesis in tea plants, increased the soluble sugar content in tea leaves (30.3%), and provided energy for the metabolic processes, including the TCA cycle, pyruvate metabolism, amino acid metabolism, and the glutamine/glutamic acid cycle, ultimately increasing the content of amino acids and antioxidant substances (catechins) in tea buds; the relative expressions of key genes for catechin synthesis, CsPAL, CsC4H, CsCHI, CsDFR, CsANS, CsANR, CsLAR, and UGGT, were significantly upregulated by 45.1-619.1%. The expressions of theanine synthesis genes CsTs, CsGs, and CsGOGAT were upregulated by 138.8-693.7%. Moreover, Se NMs promoted more sucrose transfer to the roots, with the upregulations of CsSUT1, CsSUT2, CsSUT3, and CsSWEET1a by 125.8-560.5%. Correspondingly, Se NMs enriched the beneficial rhizosphere microbiota (Roseiarcus, Acidothermus, Acidibacter, Conexicter, and Pedosphaeraceae), enhancing the absorption and utilization of ammonium nitrogen by tea plants, contributing to the accumulation of theanine. This study provides compelling evidence supporting the application of Se NMs in promoting the lipid-reducing components of tea by enhancing its nitrogen metabolism.

Both nanoplastic and iron mineral types determine their heteroaggregation: Aggregation kinetics and interface process.

Nanoplastics (NPs) inevitably interact with iron minerals (IMs) after being released into aquatic environments, changing their transport and fate. In this study, batch heteroaggregation kinetics of four types of NPs, i.e., polymethyl methacrylate (PMMA), polystyrene (PS-Bare), amino-polystyrene (PS-NH2), and carboxyl-polystyrene (PS-COOH), with two different IMs (hematite and magnetite) were conducted. We found that the heteroaggregation of NPs and IMs and the associated interfacial interaction mechanisms are both NPs-dependent and IMs-dependent. Specifically, the NPs had stronger heteroaggregation with hematite than magnetite; the heteroaggregation order of two IMs with NPs was PMMA > PS-NH2 > PS-Bare > PS-COOH. Moreover, hydrogen bond, complexation, hydrophobic, cation-π, and electrostatic interaction were involved in the interfacial reaction between NPs and hematite, and electrons were transferred from the NPs to the hematite, causing the reduction of Fe3+ into Fe2+. Furthermore, we first revealed that both pre-homoaggregation of NPs and IMs could affect their subsequent heteroaggregation, and the homoaggregates of IMs could be interrupted by PMMA or PS-COOH NPs introduction. Therefore, the emerging NPs pollution is likely to generate an ecological effect in terms of elemental cycles such as iron cycle. This work provides new insights into assessing the environmental transfer and ecological effects of NPs in aquatic environments.

Desirable Strong and Tough Adhesive Inspired by Dragonfly Wings and Plant Cell Walls.

The production of wood-based panels has a significant demand for mechanically strong and flexible biomass adhesives, serving as alternatives to nonrenewable and toxic formaldehyde-based adhesives. Nonetheless, plywood usually exhibits brittle fracture due to the inherent trade-off between rigidity and toughness, and it is susceptible to damage and deformation defects in production applications. Herein, inspired by the microstructure of dragonfly wings and the cross-linking structure of plant cell walls, a soybean meal (SM) adhesive with great strength and toughness was developed. The strategy was combined with a multiple assembly system based on the tannic acid (TA) stripping/modification of molybdenum disulfide (MoS2@TA) hybrids, phenylboronic acid/quaternary ammonium doubly functionalized chitosan (QCP), and SM. Motivated by the microstructure of dragonfly wings, MoS2@TA was tightly bonded with the SM framework through Schiff base and strong hydrogen bonding to dissipate stress energy through crack deflection, bridging, and immobilization. QCP imitated borate chemistry in plant cell walls to optimize interfacial interactions within the adhesive by borate ester bonds, boron-nitrogen coordination bonds, and electrostatic interactions and dissipate energy through sacrificial bonding. The shear strength and fracture toughness of the SM/QCP/MoS2@TA adhesive were 1.58 MPa and 0.87 J, respectively, which were 409.7% and 866.7% higher than those of the pure SM adhesive. In addition, MoS2@TA and QCP gave the adhesive good mildew resistance, durability, weatherability, and fire resistance. This bioinspired design strategy offers a viable and sustainable approach for creating multifunctional strong and tough biobased materials.

Mechanistic insight into the intensification of arsenic toxicity to rice (Oryza sativa L.) by nanoplastic: Phytohormone and glutathione metabolism modulation.

In this study, nanoplastic (NPs) at environmentally relevant concentration (0.001% w/w) had no effect on the growth of rice, while significantly elevated the phytotoxicity of As (III) by 9.4-22.8% based on the endpoints of biomass and photosynthesis. Mechanistically, NPs at 0.001% w/w enhanced As accumulation in the rice shoots and roots by 70.9% and 24.5%, respectively. Reasons of this finding can was that (1) the co-exposure with As and NPs significantly decreased abscisic acid content by 16.0% in rice, with subsequent increasing the expression of aquaporin related genes by 2.1- to 2.7-folds as compared with As alone treatment; (2) the presence of NPs significantly inhibited iron plaque formation on rice root surface by 22.5%. We firstly demonstrated that "Trojan horse effect" had no contribution to the enhancement of As accumulation by NPs exposure. Additionally, NPs disrupted the salicylic acid, jasmonic acid, and glutathione metabolism, which subsequently enhancing the oxidation (7.0%) and translocation (37.0%) of in planta As, and reducing arsenic detoxification pathways (e.g., antioxidative system (28.6-37.1%), As vacuolar sequestration (36.1%), and As efflux (18.7%)). Our findings reveal that the combined toxicity of NPs and traditional contaminations should be considered for realistic evaluations of NPs.

Development and validation of a prognostic model for cervical cancer by combination of machine learning and high-throughput sequencing.

BACKGROUND: Cervical cancer holds the highest morbidity and mortality rates among female reproductive tract tumors. However, the curative outcomes for patients with persistent, recurrent, or metastatic cervical cancer remain unsatisfactory. There is a lack of comprehensive prognostic indicators for cervical cancer. This study aims to develop a model that evaluates the prognosis of cervical cancer in combination of high-throughput sequencing and various machine learning algorithms. METHODS: In this study, we combined two single-cell RNA sequencing (scRNA-seq) projects and TCGA data for cervical cancer to obtain shared differentially expressed genes (DEGs). A LASSO regression and several learners were applied for signature feature selection. Six machine learning algorithms including Linear Discriminant Analysis, Naive Bayes, K Nearest Neighbors, Decision Tree, Random Forest, and eXtreme Gradient Boosting were utilized to construct a prognostic model for cervical cancer. External validation was conducted using the CGCI-HTMCP-CC dataset, and the accuracy of the model was assessed through ROC curve analysis. RESULTS: The results demonstrated the successful construction of a prognostic model based on DEGs from bulk- and scRNA-seq data. Ten genes CXCL8, DLC1, GRN, MPLKIP, PRDX1, RUNX1, SNX3, TFRC, UBE2V2, and UQCRC1 were screened by feature selection and applied for model construction. Random Forest exhibited the best performance in predicting the risk of cervical cancer. Patients in the high-risk group presented worse overall survival compared to those in the low-risk group. CONCLUSION: Conclusively, our model based on DEGs from bulk-seq and scRNA-seq data effectively evaluates the prognosis of cervical cancer and provides valuable insights for comprehensive clinical management.

The candidate proteins associated with keratoconus: A meta-analysis and bioinformatic analysis.

PURPOSE: Keratoconus (KC) is a multifactorial disorder. This study aimed to conduct a systematic meta-analysis to exclusively explore the candidate proteins associated with KC pathogenesis. METHODS: Relevant literature published in the last ten years in Pubmed, Web of Science, Cochrane, and Embase databases were searched. Protein expression data were presented as the standard mean difference (SMD) and 95% confidence intervals (CI). The meta-analysis is registered on PROSPERO, registration number CRD42022332442 and was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement (PRISMA). GO and KEGG enrichment analysis were performed, as well as the miRNAs and chemicals targeting the candidate proteins were predicted. PPI was analyzed to screen the hub proteins, and their expression was verified by RT-qPCR. RESULTS: A total of 21 studies were included in the meta-analysis, involving 346 normal eyes and 493 KC eyes. 18 deregulated proteins with significant SMD values were subjected to further analysis. In which, 7 proteins were up-regulated in KC compared with normal controls, including IL6 (SMD 1.54, 95%CI [0.85, 2.24]), IL1B (SMD 2.07, 95%CI [0.98, 3.16]), TNF (SMD 2.1, 95%CI [0.24, 3.96]), and MMP9 (SMD 1.96, 95%CI [0.68, 3.24]). While 11 proteins were down-regulated in KC including LOX (SMD 2.54, 95%CI [-4.51, -0.57]). GO and KEGG analysis showed that the deregulated proteins were involved in inflammation, extracellular matrix (ECM) remodeling, and apoptosis. MMP9, IL6, LOX, TNF, and IL1B were regarded as hub proteins according to the PPI analysis, and their transcription changes in stromal fibroblasts of KC were consistent with the results of the meta-analysis. Moreover, 10 miRNAs and two natural polyphenols interacting with hub proteins were identified. CONCLUSION: This study obtained 18 candidate proteins and demonstrated altered cytokine profiles, ECM remodeling, and apoptosis in KC patients through meta-analysis and bioinformatic analysis. It will provide biomarkers for further understanding of KC pathogenesis, and potential therapeutic targets for the drug treatment of KC.

3D SHINKEI MR neurography in evaluation of traumatic brachial plexus.

3D SHINKEI neurography is a new sequence for imaging the peripheral nerves. The study aims at assessing traumatic brachial plexus injury using this sequence. Fifty-eight patients with suspected trauma induced brachial plexus injury underwent MR neurography (MRN) imaging in 3D SHINKEI sequence at 3 T. Surgery and intraoperative somatosensory evoked potentials or clinical follow-up results were used as the reference standard. MRN, surgery and electromyography (EMG) findings were recorded at four levels of the brachial plexus-roots, trunks, cords and branches. Fifty-eight patients had pre- or postganglionic injury. The C5-C6 nerve postganglionic segment was the most common (average 42%) among the postganglionic injuries detected by 3D SHINKEI MRN. The diagnostic accuracy (83.75%) and the specificity (90.30%) of MRN higher than that of EMG (p < 0.001). There was no significant difference in the diagnostic sensitivity of MRN compared with EMG (p > 0.05). Eighteen patients with brachial plexus injury underwent surgical exploration after MRN examination and the correlation between MRN and surgery was 66.7%. Due to the high diagnostic accuracy and specificity, 3D SHINKEI MRN can comprehensively display the traumatic brachial plexus injury. This sequence has great potential in the accurate diagnosis of traumatic brachial plexus injury.

Inactivation of Malic Enzyme 1 in Endothelial Cells Alleviates Pulmonary Hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a progressive cardiopulmonary disease with a high mortality rate. Although growing evidence has revealed the importance of dysregulated energetic metabolism in the pathogenesis of PH, the underlying cellular and molecular mechanisms are not fully understood. In this study, we focused on ME1 (malic enzyme 1), a key enzyme linking glycolysis to the tricarboxylic acid cycle. We aimed to determine the role and mechanistic action of ME1 in PH. METHODS: Global and endothelial-specific ME1 knockout mice were used to investigate the role of ME1 in hypoxia- and SU5416/hypoxia (SuHx)-induced PH. Small hairpin RNA and ME1 enzymatic inhibitor (ME1*) were used to study the mechanism of ME1 in pulmonary artery endothelial cells. Downstream key metabolic pathways and mediators of ME1 were identified by metabolomics analysis in vivo and ME1-mediated energetic alterations were examined by Seahorse metabolic analysis in vitro. The pharmacological effect of ME1* on PH treatment was evaluated in PH animal models induced by SuHx. RESULTS: We found that ME1 protein level and enzymatic activity were highly elevated in lung tissues of patients and mice with PH, primarily in vascular endothelial cells. Global knockout of ME1 protected mice from developing hypoxia- or SuHx-induced PH. Endothelial-specific ME1 deletion similarly attenuated pulmonary vascular remodeling and PH development in mice, suggesting a critical role of endothelial ME1 in PH. Mechanistic studies revealed that ME1 inhibition promoted downstream adenosine production and activated A2AR-mediated adenosine signaling, which leads to an increase in nitric oxide generation and a decrease in proinflammatory molecule expression in endothelial cells. ME1 inhibition activated adenosine production in an ATP-dependent manner through regulating malate-aspartate NADH (nicotinamide adenine dinucleotide plus hydrogen) shuttle and thereby balancing oxidative phosphorylation and glycolysis. Pharmacological inactivation of ME1 attenuated the progression of PH in both preventive and therapeutic settings by promoting adenosine production in vivo. CONCLUSIONS: Our findings indicate that ME1 upregulation in endothelial cells plays a causative role in PH development by negatively regulating adenosine production and subsequently dysregulating endothelial functions. Our findings also suggest that ME1 may represent as a novel pharmacological target for upregulating protective adenosine signaling in PH therapy.

Pivotal Role of GSTO2 in Ferroptotic Neuronal Injury After Intracerebral Hemorrhage.

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.

Intestinal tuberculosis with small bowel stricture and hemorrhage as the predominant manifestation: Three case reports.

BACKGROUND: Intestinal tuberculosis is a chronic disease caused by Mycobacterium tuberculosis that mainly affects the ileum and cecum. Small bowel tuberculosis, characterized by predominant involvement of the small intestine, is an extremely rare condition with highly atypical clinical presentations, making diagnosis even more challenging. CASE SUMMARY: We report three cases of small intestinal tuberculosis, two of the patients presented primarily with abdominal pain, and one presented with gastrointestinal bleeding. All patients underwent blood tests and imaging examinations. Small bowel endoscopy (SBE) revealed that the main lesions in these patients were intestinal stenosis or gastrointestinal bleeding caused by small intestinal ulcers. One patient ultimately underwent surgical treatment. Following a complex diagnostic process and comprehensive analysis, all patients were confirmed to have small intestinal tuberculosis and received standard antituberculosis treatment, leading to an improvement in their condition. CONCLUSION: Patients with SBTs present with nonspecific symptoms such as abdominal pain, weight loss, and occasional gastrointestinal bleeding. Accurate diagnosis requires a thorough evaluation of clinical symptoms and various tests to avoid misdiagnosis and complications.

Tough physically crosslinked poly(vinyl alcohol)-based hydrogels loaded with collagen type I to promote bone regeneration in vitro and in vivo.

Poly(vinyl alcohol) (PVA) hydrogels exhibit great potential as ideal biomaterials for tissue engineering, owing to their non-toxicity, high water content, and strong biocompatibility. However, limited mechanical strength and low bioactivity have constrained their application in bone tissue engineering. In this study, we have developed a tough PVA-based hydrogel using a facile physical crosslinking method, comprising of PVA, tannic acid (TA), and hydroxyapatite (HA). Systematic experiments were conducted to examine the physicochemical properties of PVA/HA/TA hydrogels, including their compositions, microstructures, and mechanical and rheological properties. The results demonstrated that the PVA/HA/TA hydrogels possessed the porous microstructures and excellent mechanical properties. Furthermore, collagen type I (ColI) was used to further improve the biocompatibility and bioactivity of PVA/HA/TA hydrogels. In vitro experiments revealed that PVA/HA/TA/COL hydrogel could offer a suitable microenvironment for the growth of MC3T3-E1 cells and promote their osteogenic differentiation. Meanwhile, the PVA/HA/TA/COL hydrogel demonstrated the ability to promote bone regeneration and osteointegration in a rat femoral defect model. This study provides a potential strategy for the use of PVA-based hydrogels in bone tissue engineering.

Noninvasive Monitoring of Immunotherapy in Lung Cancer by Lymphocyte Activation Gene 3 PET Imaging of Tumor-Infiltrating Lymphocytes.

Although immunotherapy has revolutionized the entire cancer treatment landscape, small fractions of patients respond to immunotherapy. Early identification of responders may improve patient management during immunotherapy. In this study, we evaluated a PET approach for monitoring immunotherapy in lung cancer by imaging the upregulation of lymphocyte activation gene 3 (LAG-3)-expressing (LAG-3+) tumor-infiltrating lymphocytes (TILs). Methods: We synthesized a LAG-3-targeted molecular imaging probe, [68Ga]Ga-NOTA-C25 and performed a series of in vitro and in vivo assays to test its specificity. Next, [68Ga]Ga-NOTA-C25 PET was used to monitor immunotherapy in murine lung cancer-bearing mice and in humanized mouse models for assessing clinical translational potential, with confirmation by immunostaining and flow cytometry analysis. Results: [68Ga]Ga-NOTA-C25 PET could noninvasively detect intertumoral differences in LAG-3+ TIL levels in different tumor models. Importantly, in Lewis lung carcinoma tumor models treated with an agonist of a stimulator of interferon genes, [68Ga]Ga-NOTA-C25 PET also detected an immunophenotyping transition of the tumor from "cold" to "hot" before changes in tumor size. Meanwhile, animals carrying "hot" tumor showed more significant tumor inhibition and longer survival than those carrying "cold" tumor. [68Ga]Ga-NOTA-C25 PET also showed markedly higher tumor uptake in immune system-humanized mice carrying human non-small cell lung cancer than immunodeficient models. Conclusion: [68Ga]Ga-NOTA-C25 PET could be used to noninvasively monitor the early response to immunotherapy by imaging LAG-3+ TILs in lung cancer. [68Ga]Ga-NOTA-C25 PET also exhibited excellent translational potential, with great significance for the precise management of lung cancer patients receiving immunotherapy.

SAH and SAM/SAH ratio associate with acute kidney injury in critically ill patients: A case-control study.

BACKGROUND: Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression and poor prognosis, which has high morbidity and mortality in hospitalized patients. DNA methylation plays an important role in the occurrence and progression of kidney disease, and aberrant methylation and certain altered methylation-related metabolites have been reported in AKI patients. However, the specific alterations of methylation-related metabolites in the AKI patients were not investigated clearly. METHOD: In this study, 61 AKI and 61 matched non-AKI inpatients were recruited after propensity score matching the age and hypertension. And 11 methylation-related metabolites in the plasma and urine of the two groups were quantified by using UHPLC-MS/MS method. RESULTS: Certain methylation-relate intermediates were up-regulated in the plasma (choline, trimethylamine N-oxide (TMAO), trimethyl lysine (TML), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)) and down-regulated in the urine of AKI inpatients (choline, betaine, TMAO, dimethylglycine (DMG), SAM and taurine). The correlation analysis revealed a relatively strong correlation between plasma SAH, SAM/SAH ratio and renal function index (serum creatinine (SCr) and estimated glomerular filtration rate (eGFR), r = 0.523-0.616), and the correlation of urinary intermediates with renal function index was weaker than that in the plasma. Furthermore, receiver operating characteristic (ROC) analysis showed that plasma SAH and urinary SAM/SAH ratio represented the best distinguishing efficiency with AUC 0.844 and 0.794, respectively. Moreover, the findings of binary regression analysis demonstrated plasma choline, TMAO, TML, SAM and SAH were the risk markers of AKI (up-regulation in plasma, OR > 1), urinary choline, betaine, TMAO, DMG and SAM were protective markers of AKI (down-regulation in urine, OR < 1), and SAM/SAH ratio was a protective marker in plasma and urine (down-regulation in both two biofluids, OR = 0.510, 0.383-0.678 in plasma, OR = 0.904, 0.854-0.968 in urine), indicating the increased risk of AKI when combined with the alteration of plasma and urinary levels. CONCLUSION: The comprehensive analysis of plasma and urine samples from AKI inpatients offers a more extensive assessment of methylated metabolic alterations, suggesting a close relationship between AKI stress and altered methylation ability. The plasma level of SAH and SAM/SAH ratio and urinary SAM/SAH ratio both showed a strong correlation with renal function (SCr and eGFR) and good accuracy for distinguishing AKI in the two biomatrices, which exhibited promising prospects in predicting renal function decline and providing further information for the pathogenesis of AKI.

Stevens-Johnson syndrome secondary to massive inflammatory hyperplasia of bilateral lingual margins: a case report and literature review.

Stevens-Johnson syndrome (SJS), also known as the multifactorial erythematous drug eruption, is a class of adverse reactions of the skin and mucous membranes primarily caused by drug allergy often involving the oral cavity, eyes, and external genital mucosa, generally accompanied by fever, and can be life-threatening in severe cases. In February 2022, the Department of Stomatology, the First Affiliated Hospital of Zhengzhou University admitted a patient with huge inflammatory hyperplasia of bilateral lingual margins secondary to SJS. Upon admission, no other obvious symptoms were observed except for tongue hyperplasia. The patient suffered from a severe adverse drug reaction caused by acetaminophen 2 months ago and was complicated by liver dysfunction and pulmonary infection. After 1 month of treatment and rehabilitation, he developed a secondary tongue mass and was subsequently admitted to Dept. of Oral and Maxillofacial Surgery Ward 2, the First Affiliated Hospital of Zhengzhou University. After completing the examination, the tongue mass was surgically removed. After a follow-up of 11 months, the patient's condition was satisfactory and no temporary discomfort was observed. The case of tongue mass secondary to SJS is extremely rare. If a stomatologist encounters a similar case, we should carefully inquire about the drug allergy history and recent medication history, and be alert to whether or not they had adverse drug reactions recently.