Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis.

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy-saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide-induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

Development of high-efficiency superparamagnetic drug delivery system with MPI imaging capability.

In this study, a high-efficiency superparamagnetic drug delivery system was developed for preclinical treatment of bladder cancer in small animals. Two types of nanoparticles with magnetic particle imaging (MPI) capability, i.e., single- and multi-core superparamagnetic iron oxide nanoparticles (SPIONs), were selected and coupled with bladder anti-tumor drugs by a covalent coupling scheme. Owing to the minimal particle size, magnetic field strengths of 270 mT with a gradient of 3.2 T/m and 260 mT with a gradient of 3.7 T/m were found to be necessary to reach an average velocity of 2 mm/s for single- and multi-core SPIONs, respectively. To achieve this, a method of constructing an in vitro magnetic field for drug delivery was developed based on hollow multi-coils arranged coaxially in close rows, and magnetic field simulation was used to study the laws of the influence of the coil structure and parameters on the magnetic field. Using this method, a magnetic drug delivery system of single-core SPIONs was developed for rabbit bladder therapy. The delivery system consisted of three coaxially and equidistantly arranged coils with an inner diameter of Φ50 mm, radial height of 85 mm, and width of 15 mm that were positioned in close proximity to each other. CCK8 experimental results showed that the three types of drug-coupled SPION killed tumor cells effectively. By adjusting the axial and radial positions of the rabbit bladder within the inner hole of the delivery coil structure, the magnetic drugs injected could undergo two-dimensional delivery motions and were delivered and aggregated to the specified target location within 12 s, with an aggregation range of about 5 mm × 5 mm. In addition, the SPION distribution before and after delivery was imaged using a home-made open-bore MPI system that could realistically reflect the physical state. This study contributes to the development of local, rapid, and precise drug delivery and the visualization of this process during cancer therapy, and further research on MPI/delivery synchronization technology is planned for the future.

Targeting SIGLEC15 as an emerging immunotherapy for anaplastic thyroid cancer.

Anaplastic thyroid carcinoma (ATC) is the most aggressive subtype of thyroid cancer with few effective therapies. Though immunotherapies such as targeting PD-1/PD-L1 axis have benefited patients with solid tumor, the druggable immune checkpoints are quite limited in ATC. In our study, we focused on the anti-tumor potential of sialic acid-binding Ig-like lectins (Siglecs) in ATC. Through screening by integrating microarray datasets including 216 thyroid-cancer tissues and single-cell RNA-sequencing, SIGLEC family members CD33, SIGLEC1, SIGLEC10 and SIGLEC15 were significantly overexpressed in ATC, among which SIGLEC15 increased highest and mainly expressed on cancer cells. SIGLEC15high ATC cells are characterized by high expression of serine protease PRSS23 and cancer stem cell marker CD44. Compared with SIGLEC15low cancer cells, SIGLEC15high ATC cells exhibited higher interaction frequency with tumor microenvironment cells. Further study showed that SIGLEC15high cancer cells mainly interacted with T cells by immunosuppressive signals such as MIF-TNFRSF14 and CXCL12-CXCR4. Notably, treatment of anti-SIGLEC15 antibody profoundly increased the cytotoxic ability of CD8+ T cells in a co-culture model and zebrafish-derived ATC xenografts. Consistently, administration of anti-SIGLEC15 antibody significantly inhibited tumor growth and prolonged mouse survival in an immunocompetent model of murine ATC, which was associated with increase of M1/M2, natural killer (NK) cells and CD8+ T cells, and decrease of myeloid-derived suppressor cells (MDSCs). SIGLEC15 inhibited T cell activation by reducing NFAT1, NFAT2, and NF-κB signals. Blocking SIGLEC15 increased the secretion of IFN-γ and IL-2 in vitro and in vivo. In conclusion, our finding demonstrates that SIGLEC15 is an emerging and promising target for immunotherapy in ATC.

Dynamic changes in the non-volatile and flavour compounds in withered tea leaves of three different colour cultivars based on multi-omics.

In this study, metabolomics and proteomics were performed to investigate the fluctuations of non-volatile compounds and proteins in tea leaves from three tea cultivars with varying colours during withering. A total of 2798 compounds were detected, exhibiting considerable variations in amino acids, phenylpropanoids, and flavonoids. The ZH1 cultivar displayed increased levels of amino acids but decreased levels of polyphenols, which might be associated with the up-regulation of enzymes responsible for protein degradation and subsequent amino acid production, as well as the down-regulation of enzymes involved in phenylpropanoid and flavonoid biosynthesis. The FUD and ZH1 cultivars had elevated levels of flavanols and flavanol-O-glycosides, which were regulated by the upregulation of FLS. The ZJ and ZH1 cultivars displayed elevated levels of theaflavin and peroxidase. This work presents a novel investigation into the alterations of metabolites and proteins between tea cultivars during withering, and helps with the tea cultivar selection and manufacturing development.

[Effects of Water Level Fluctuations and Vegetation Restoration on Soil Prokaryotic Microbial Community Structure in the Riparian Zone of the Three Gorges Reservoir].

Riparian zones are typical fragile and sensitive ecological areas. Fluctuations in water level are the main factor affecting the soil environment in these zones, and vegetation restoration is considered an important means of soil conservation there. However, the interactive effects of water level fluctuations and vegetation restoration on the soil microbial community structure in the reservoir riparian zone remain unclear. Therefore, we selected abandoned grassland and artificial forestland at different water level elevations as research objects in the riparian zone of the Three Gorges Reservoir. We used 16S rRNA high-throughput sequencing technology to explore the composition and diversity of soil prokaryotic microbial communities and investigated the main environmental factors driving the soil microbial community structure. The results showed that the α diversity of soil prokaryotes was the highest at the low water level of the riparian zone. The Pielou_e index, Shannon index, and Simpson index at the 163 m elevation were significantly higher than those at the 168 m elevation, and the Chao1 index and Shannon index were significantly higher than those at the 173 m elevation. However, no significant difference was found in the soil microbial community α diversity between abandoned grassland and artificial forestland. At the same time, water level fluctuations and vegetation restoration had significant effects on the community composition of soil prokaryotic microorganisms, and there were significant differences in biomarker categories in different study sites. Notably, the effects of vegetation restoration types on the soil prokaryotic microbial community structure were stronger than that of water level fluctuations. In addition, the results of hierarchical segmentation showed that soil pH was the main driving factor for the change in soil prokaryotic microbial community structure in the Three Gorges Reservoir. These results deepen our understanding of the variations in microbial community structure in the reservoir riparian zone and provide scientific reference for the restoration and reconstruction of the riparian zone ecosystem.

The association in diabetic retinopathy and stroke finding from NHANES evidence.

PURPOSE: Diabetic retinopathy and stroke are both vascular pathologies, and this study intends to investigate the relationship between diabetic retinopathy and stroke. METHODS: The NHANES database was used to find the relationship between diabetic retinopathy and stroke with 1948 individuals aged 40 years or older. The sensitivity of the data was verified by multiple interpolation, further analysis was done by subgroup analyses, and possible links were investigated with mediation studies. RESULTS: Diabetes retinopathy was found to be closely associated with stroke, with the PDR group having a higher stroke incidence than the NPDR group. After controlling for covariates, there were still substantial differences in the risk of stroke among patients with NPDR and PDR. Overall, subgroup analysis revealed DR group showed an important distinction, compared to the non-DR (OR = 1.76, 95% CI 1.15-2.64). The results of the mediation research indicated that the connection between DR and stroke was mediated by the frailty index and hypertension. CONCLUSION: This study demonstrated a statistically significant correlation between DR and stroke, which persisted even after DR staging and was more prevalent in PDR patients than in NPDR patients. Stroke prevention may benefit from DR health management.

Disrupting glycolysis and DNA repair in anaplastic thyroid cancer with nucleus-targeting platinum nanoclusters.

Cancer cells rely on aerobic glycolysis and DNA repair signals to drive tumor growth and develop drug resistance. Yet, fine-tuning aerobic glycolysis with the assist of nanotechnology, for example, dampening lactate dehydrogenase (LDH) for cancer cell metabolic reprograming remains to be investigated. Here we focus on anaplastic thyroid cancer (ATC) as an extremely malignant cancer with the high expression of LDH, and develop a pH-responsive and nucleus-targeting platinum nanocluster (Pt@TAT/sPEG) to simultaneously targets LDH and exacerbates DNA damage. Pt@TAT/sPEG effectively disrupts LDH activity, reducing lactate production and ATP levels, and meanwhile induces ROS production, DNA damage, and apoptosis in ATC tumor cells. We found Pt@TAT/sPEG also blocks nucleotide excision repair pathway and achieves effective tumor cell killing. In an orthotopic ATC xenograft model, Pt@TAT/sPEG demonstrates superior tumor growth suppression compared to Pt@sPEG and cisplatin. This nanostrategy offers a feasible approach to simultaneously inhibit glycolysis and DNA repair for metabolic reprogramming and enhanced tumor chemotherapy.

Neuropilin-1 enhances temozolomide resistance in glioblastoma via the STAT1/p53/p21 axis.

Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.

Protective effect of Xixin-Ganjiang herb pair for warming the lungs to dissolve phlegm in chronic obstructive pulmonary disease rats based on integrated network pharmacology and metabolomics.

Xixin-Ganjiang herb pair (XGHP) is a classic combination for warming the lungs to dissolve phlegm and is often used to treat a variety of chronic lung diseases; it can treat the syndrome of cold phlegm obstruction of lungs. First, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to examine the composition of XGHP, and network pharmacology was used to predict its potential core targets and signaling pathways in the current study. Second, a rat model of chronic obstructive pulmonary disease (COPD) was established for assessing the anti-COPD activity of XGHP, and metabolomics was used to explore the biomarkers and metabolic pathways. Finally, the sample was validated using molecular docking and Western blotting. The integration of metabolomics and network pharmacology results identified 11 targets, 3 biomarkers, 3 pathways, and 2 metabolic pathways. Western blotting showed that XGHP effectively regulated the expression of core proteins via multiple signaling pathways (downregulation of toll-like receptor 4 [TLR4] and upregulation of serine/threonine-protein kinase 1 [p-AKT1] and nitric oxide synthase 3 [NOS3]). Molecular docking results showed that the 10 potentially active components of XGHP have good affinity with tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase 9 (MMP-9), TLR4, p-AKT1, and NOS3. Our findings suggest that XGHP may regulate glucolipid metabolism, improve energy supply, and inhibit inflammatory responses (TNF-α, IL-6, and MMP-9) via the PI3K-Akt signaling pathway and HIF-1 signaling pathway in the management of COPD.

Vitamin D, selenium, and antidiabetic drugs in the treatment of type 2 diabetes mellitus with Hashimoto's thyroiditis.

BACKGROUND: Diabetes and thyroiditis are closely related. They occur in combination and cause significant damage to the body. There is no clear treatment for type-2 diabetes mellitus (T2DM) with Hashimoto's thyroiditis (HT). While single symptomatic drug treatment of the two diseases is less effective, combined drug treatment may improve efficacy. AIM: To investigate the effect of a combination of vitamin D, selenium, and hypo-glycemic agents in T2DM with HT. METHODS: This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023. Fifty patients were assigned to the control group, test group A, and test group B according to different treatment methods. The control group received low-iodine diet guidance and hypoglycemic drug treatment. Test group A received the control treatment plus vitamin D treatment. Test group B received the group A treatment plus selenium. Blood levels of markers of thyroid function [free T3 (FT3), thyroid stimulating hormone (TSH), free T4 (FT4)], autoantibodies [thyroid peroxidase antibody (TPOAB) and thyroid globulin antibody (TGAB)], blood lipid index [low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triacylglycerol (TG)], blood glucose index [fasting blood glucose (FBG), and hemoglobin A1c (HbA1c)] were measured pre-treatment and 3 and 6 months after treatment. The relationships between serum 25-hydroxyvitamin D3 [25 (OH) D3] level and each of these indices were analyzed. RESULTS: The levels of 25 (OH) D3, FT3, FT4, and LDL-C increased in the order of the control group, test group A, and test group B (all P < 0.05). The TPOAB, TGAB, TC, TG, FBG, HbA1c, and TSH levels increased in the order of test groups B, A, and the control group (all P < 0.05). All the above indices were compared after 3 and 6 months of treatment. Pre-treatment, there was no divergence in serum 25 (OH) D3 level, thyroid function-related indexes, autoantibodies level, blood glucose, and blood lipid index between the control group, test groups A and B (all P > 0.05). The 25 (OH) D3 levels in test groups A and B were negatively correlated with FT4 and TGAB (all P < 0.05). CONCLUSION: The combination drug treatment for T2DM with HT significantly improved thyroid function, autoantibody, and blood glucose and lipid levels.

Targeting DEP domain containing 1 in anaplastic thyroid carcinoma: Implications for stemness regulation and malignant phenotype suppression.

Background: Anaplastic thyroid carcinoma (ATC), a rare but highly aggressive endocrine malignancy, is characterized by a significant presence of cancer stem-like cells (CSCs). These CSCs, known for their self-renewal and differentiation capacities, contribute to various aggressive tumor properties, including recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Despite their critical role, the regulatory mechanisms of CSCs in ATC remain poorly elucidated, posing challenges in effectively targeting these cells for treatment. Methods: To delve into this, we employed the single sample gene set enrichment analysis (ssGSEA) algorithm to evaluate the stemness of samples in combined datasets. Samples were then classified into high and low stemness subgroups based on their average stemness scores. Differential gene expression between these subgroups was analyzed. We further explored the association of candidate genes with patient prognosis. Additionally, we conducted gene set enrichment analysis (GSEA) and a series of cell biology experiments to validate the role of DEP domain-containing protein 1 (DEPDC1) in fostering CSC-like traits and regulating the malignant phenotypes of ATC. Results: Our investigation demonstrated that DEPDC1 was significantly upregulated in CSCs and is abundantly expressed in ATC tissues. In vitro assays revealed that knockdown of DEPDC1 markedly inhibited tumor sphere formation and attenuated the proliferation, invasion, and migration of ATC cells. This silencing also resulted in reduced expression of stemness markers associated with CSCs. Furthermore, our GSEA findings linked high DEPDC1 expression to cell cycle progression and the maintenance of tumor cell stemness, with DEPDC1 knockdown disrupting these signaling pathways. Collectively, our results position DEPDC1 as a pivotal regulator of CSC-like characteristics in ATC, where aberrant DEPDC1 expression amplifies stemness properties and fuels the cancer's aggressive behavior. Consequently, DEPDC1 emerges as a promising therapeutic target for ATC management. In summary, this study underscores the pivotal role of DEPDC1 in modulating CSC-like features in ATC, offering new avenues for targeted therapy in this challenging malignancy.

IGSF8 is a potential target for the treatment of Gliomas.

BACKGROUND: Immunoglobulin superfamily member 8, or IGSF8, is a member of the recently identified immunoglobulin family of proteins. It is mostly produced on cell membranes and has a unique transmembrane structure. It has recently been demonstrated that there is a strong correlation between the expression variation of IGSF8 and the growth of gliomas. Therefore, we used data from the TCGA and CGGA databases to evaluate the function of IGSF8. METHODS: The TCGA and GTEx data sets' RNA-seq data were utilized to examine IGSF8 expression. The Gene Cards database was utilized to get IGSF8 protein data. The Cluster Profiler data package was used to carry out the IGSF8 enrichment study. The GO and KEGG databases were used to examine the relationship between IGSF8 and cellular physiological and biochemical processes. The TCGA immune cell infiltration scores were obtained from online databases and published studies. Clinical survival data from TCGA and CGGA were used to investigate the predictive significance of IGSF8. RESULTS: TGGA revealed that the majority of cancers had differential expression of IGSF8. IGSF8 was discovered to be enriched in numerous significant pathways in tumor cells by GO and KEGG. Moreover, a strong correlation was seen between the expression of IGSF8 and the immunomodulatory interactions that occur between non-lymphocytes and lymphocytes. T-cell infiltration, immunological checkpoints, immune-activating and immune-suppressive genes, chemokines, and chemokine receptors were all strongly correlated with IGSF8 expression. Lastly, the TCGA and CGGA databases showed a strong correlation between IGSF8 and the grade and prognosis of gliomas. CONCLUSION: According to our findings, IGSF8 may be a glioma marker. In order to control the immunological microenvironment, IGSF8 may cooperate with a number of immune checkpoints. This information may be utilized to create novel targeted immunotherapy medications.

Different dose aspirin plus immunoglobulin (DAPI) for prevention of coronary artery abnormalities in Kawasaki disease: Study protocol for a multi-center, prospective, randomized, open-label, blinded end-point, non-inferiority trial.

BACKGROUND: Kawasaki disease is a pediatric acute systemic vasculitis that specifically involves the coronary arteries. Timely initiation of immunoglobulin plus aspirin is necessary for diminishing the incidence of coronary artery abnormalities (CAAs). The optimal dose of aspirin, however, remains controversial. The trial aims to evaluate if low-dose aspirin is noninferior to moderate-dose in reducing the risk of CAAs during the initial treatment of Kawasaki disease. METHODS: This is a multi-center, prospective, randomized, open-label, blinded endpoint, noninferiority trial to be conducted in China. The planned study duration is from 2023 to 2026. Data will be analyzed according to intention-to-treat principles. Participants are children and adolescents under the age of 18 with Kawasaki disease, recruited from the inpatient units. A sample size of 1,346 participants will provide 80% power with a one-sided significance level of 0.025. Qualifying children will be randomized (1:1) to receive either intravenous immunoglobulin (2 g/kg) plus oral moderate-dose aspirin (30-50 mg·kg-1·d-1) until the patient is afebrile for at least 48 hours, or immunoglobulin plus low-dose aspirin (3-5 mg·kg-1·d-1) as initial treatment. The primary outcome will be the occurrence of CAAs at 8 weeks after immunoglobulin infusion. Independent blinded pediatric cardiologists will assess the primary endpoint using echocardiography. CONCLUSIONS: There is a shortage of consensus on the dose of aspirin therapy for Kawasaki disease due to the lack of evidence. The results of our randomized trial will provide more concrete evidence for the efficacy and adverse events of low- or moderate-dose aspirin in the acute phase of Kawasaki disease. TRIAL REGISTRATION: www.chictr.org.cn: ChiCTR2300072686.

Shedding light on ONOO- detection: the emergence of a fast-response fluorescent probe for biological systems.

ONOO-, a bioactive molecule, plays a critical role in inflammation-related signaling pathways and pathological mechanisms. Numerous studies have established a direct correlation between elevated ONOO- levels and tumor progression. Therefore, investigating ONOO- levels in inflammation and tumors is of utmost importance. Fluorescence imaging presents a highly sensitive, non-invasive, easily operable, selective, and efficient method for ONOO- detection in situ. In this study, we designed and synthesized a rhodamine-based probe, NRho, which effectively identifies tumors, inflammatory cells, tissues, and organs by detecting ONOO- content. The synthesis process of NRho is simple, yielding a probe with favorable spectral characteristics and rapid response. Our cell imaging analysis has provided novel insights, revealing distinct ONOO- levels among different types of cancer cells, with hepatocellular carcinoma cells exhibiting higher ONOO- content than the others. This observation marks the proposal of such variations in ONOO- levels across cancer cell types. Furthermore, our study has showcased the practicality of our probe in live organ imaging, enabling the identification of tumors from living organs within a brief 5-minute incubation period. Additionally, our findings highlight the rapid detection capability of the probe NRho in various tissue samples, effectively identifying inflammation. This research holds important promise in advancing biomedical research and clinical diagnosis.

Ferroptosis-Related Genes Are Associated with Radioresistance and Immune Suppression in Head and Neck Cancer.

Background: Ferroptosis is associated with tumor development; however, its contribution to radioresistant head and neck cancer (HNC) remains unclear. In this study, we used bioinformatics analysis and in vitro testing to explore ferroptosis-related genes associated with HNCs radiosensitivity. Materials and Methods: GSE9714, GSE90761, and The Cancer Genome Atlas (TCGA) datasets were searched to identify ferroptosis-related differentially expressed genes between radioresistant and radiosensitive HNCs or radiation-treated and nonradiation-treated HNCs. A protein-protein interaction analysis on identified hub genes was then performed. Receiver operating characteristic curves and Kaplan-Meier survival analysis were used to assess the diagnostic and prognostic potential of the hub genes. Cell counting kit-8, transwell assay, and flow cytometry were applied to examine the role of hub gene collagen type IV, alpha1 chain (COL4A1) on the proliferation, migration, invasion, and apoptosis of TU686 cells. Results: Hub genes MMP10, MMP1, COL4A1, IFI27, and INHBA showed diagnostic potential for HNC and were negatively correlated with overall survival and disease-free survival in the TCGA dataset. Also, IL-1B, IFI27, INHBA, and COL4A1 mRNA levels were significantly increased in TCGA patients with advanced clinical stages or receiving radiotherapy, whereas COL4A1, MMP10, and INHBA expressions were negatively correlated with immune infiltration. Furthermore, the knockdown of COL4A1 inhibited cell proliferation, migration, and invasion while promoting apoptosis in TU686 cells. Conclusion: Ferroptosis-related hub genes, such as COL4A1, are potential diagnostic and prognostic indicators as well as therapeutic targets for HNC.

Application of intentional replantation in advanced periodontitis involving teeth preservation.

With the development of periodontal regenerative technology, an increasing number of scholars reported that advanced periodontitis involving teeth can be preserved through intentional replantation. Intentional replantation has become the last possible method to preserve natural teeth for advance periodontitis with signs of tooth extraction. However, the indications of intentional replantation are strict, and the success of the operation is closely related to the condition of cases and the operation skills of doctors. In this article, the operation steps and criteria of intentional replantation were summarized by introducing three success cases of advanced periodontitis involving teeth preserved by intentional replantation. The relevant factors that affect the prognosis of intentional replantation in advanced periodontitis involving teeth preservation were analyzed to help clinicians preserve natural teeth.

Family members' experiences of bereavement in the emergency department: A meta-synthesis of qualitative studies.

The emergency department (ED) is one of the places where patient deaths frequently occur. Understanding family members' experiences of bereavement would help provide individualized bereavement care. We conducted a meta-synthesis to synthesize family members' experiences of bereavement in the ED and assess the impact of bereavement on their lives. We searched seven international electronic databases. Five studies were selected and critically appraised. Thematic analysis was employed. Five themes (with 13 subthemes) were derived: suffering sudden changes and are severely impacted, multiple feelings and needs of waiting, final farewell, personal and family difficulties after leaving the ED, and journey through grief. Family members endured agonizing waits to see and learn more about their family members' condition. Family members reported the need for effective follow-up resources. Findings revealed that it would be helpful if the EDs could provide sensitive and respectful care to family members.

Recyclable and Stable Porphyrin-Based Self-Assemblies by Electrostatic Force for Efficient Photocatalytic Organic Transformation.

Development of efficient, stable, and recyclable photocatalysts for organic synthesis is vital for transformation of traditional thermal organic chemistry into green sustainable organic chemistry. In this work, the study reports an electrostatic approach to assemble meso-tetra (4-sulfonate phenyl) porphyrin (TPPS)tetra (4-sulfonate phenyl) porphyrin (TPPS) as a donor and benzyl viologen (BV) as an acceptor into stable and recyclable photocatalyst for an efficient organic transformation reaction - aryl sulfide oxidation. By use of the electrostatic TPPS-BV photocatalysts, 0.1 mmol aryl sulfide with electron-donating group can be completely transformed into aryl sulfoxide in 60 min without overoxidation into sulfone, rendering near 100% yield and selectivity. The photocatalyst can be recycled up to 95% when 10 mg amount is used. Mechanistic study reveals that efficient charge separation between TPPS and BV results in sufficient formation of superoxide which further reacts with the oxidized sulfide by the photocatalyst to produce the sulfoxide. This mechanistic pathway differs significantly from the previously proposed singlet oxygen-dominated process in homogeneous TPPS photocatalysis.

Switching the proton-coupled electron transfer mechanism for non-canonical tyrosine residues in a de novo protein.

The proton-coupled electron transfer (PCET) reactions of tyrosine (Y) are instrumental to many redox reactions in nature. This study investigates how the local environment and the thermodynamic properties of Y influence its PCET characteristics. Herein, 2- and 4-mercaptophenol (MP) are placed in the well-folded α3C protein (forming 2MP-α3C and 4MP-α3C) and oxidized by external light-generated [Ru(L)3]3+ complexes. The resulting neutral radicals are long-lived (>100 s) with distinct optical and EPR spectra. Calculated spin-density distributions are similar to canonical Y˙ and display very little spin on the S-S bridge that ligates the MPs to C32 inside the protein. With 2MP-α3C and 4MP-α3C we probe how proton transfer (PT) affects the PCET rate constants and mechanisms by varying the degree of solvent exposure or the potential to form an internal hydrogen bond. Solution NMR ensemble structures confirmed our intended design by displaying a major difference in the phenol OH solvent accessible surface area (≤∼2% for 2MP and 30-40% for 4MP). Additionally, 2MP-C32 is within hydrogen bonding distance to a nearby glutamate (average O-O distance is 3.2 ± 0.5 Å), which is suggested also by quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations. Neither increased exposure of the phenol OH to solvent (buffered water), nor the internal hydrogen bond, was found to significantly affect the PCET rates. However, the lower phenol pKa values associated with the MP-α3C proteins compared to α3Y provided a sufficient change in PT driving force to alter the PCET mechanism. The PCET mechanism for 2MP-α3C and 4MP-α3C with moderately strong oxidants was predominantly step-wise PTET for pH values, but changed to concerted PCET at neutral pH values and below when a stronger oxidant was used, as found previously for α3Y. This shows how the balance of ET and PT driving forces is critical for controlling PCET mechanisms. The presented results improve our general understanding of amino-acid based PCET in enzymes.

The Cooperation Regulation of Antioxidative System and Hormone Contents on Physiological Responses of Wedelia trilobata and Wedelia chinensis under Simulated Drought Environment.

Drought-induced metabolic dysregulation significantly enhances the production of reactive oxygen species (ROS), which, in turn, exerts a substantial influence on the oxidation-reduction regulatory status of cells. These ROS, under conditions of drought stress, become highly reactive entities capable of targeting various plant organelles, metabolites, and molecules. Consequently, disruption affects a wide array of metabolic pathways and eventually leads to the demise of the cells. Given this understanding, this study aimed to investigate the effects of different drought stress levels on the growth and development of the invasive weed Wedelia trilobata and its co-responding native counterpart Wedelia chinensis. Both plants evolved their defense mechanisms to increase their antioxidants and hormone contents to detoxify ROS to avoid oxidative damage. Still, the chlorophyll content fluctuated and increased in a polyethylene-glycol-simulated drought. The proline content also rose in the plants, but W. chinensis showed a significant negative correlation between proline and malondialdehyde in different plant parts. Thus, W. trilobata and W. chinensis exhibited diverse or unlike endogenous hormone regulation patterns under drought conditions. Meanwhile, W. trilobata and W. chinensis pointedly increased the content of indole acetic acid and gibberellic acid in a different drought stress environment. A positive correlation was found between endogenous hormones in other plant parts, including in the roots and leaves. Both simulated and natural drought conditions exerted a significant influence on both plant species, with W. trilobata displaying superior adaptation characterized by enhanced growth, bolstered antioxidant defense mechanisms, and heightened hormonal activities.