Causal associations between the gut microbiota and multiple myeloma: a two-sample Mendelian randomization study.

Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Red-Light Triggered H-Abstraction Photoinitiators for the Efficient Oxygen-Independent Therapy of Hypoxic Tumors.

The clinical application of photodynamic therapy (PDT) is limited by oxygen-dependence and side effects caused by photosensitizer residues. Photoinitiators based on the H-abstraction reaction can address these challenges because they can generate alkyl radical-killing cells independently of oxygen and undergo rapid bleaching following H-abstraction. Nonetheless, the development of photoinitiators for PDT has been impeded by the absence of effective design strategies. Herein, we have developed aryl-ketone substituted cyanine (ACy-R), the first red-light triggered H-abstraction photoinitiators for hypoxic cancer therapy. These ACy-R molecules inherited the near-infrared absorption of cyanine dye, and aryl-ketone modification imparted H-abstraction capability. Experimental and quantum calculations revealed that modifying the electron-withdrawing groups of the aryl (e.g., ACy-5F) improved the contribution of the O atom to the photon excitation process promoting intersystem crossing and H-abstraction ability. Particularly, ACy-5F rapidly penetrated cells and enriched in the endoplasmic reticulum. Even under severe hypoxia, ACy-5F initiated red-light induced H-abstraction with intracellular biomolecules, inducing necroptosis and ferroptosis. Moreover, ACy-5F was degraded after H-abstraction, thus avoiding the side effects of long-term phototoxicity after therapy. This study not only provides a crucial molecular tool for hypoxic tumors therapy, but also presents a promising strategy for the development of multifunctional photosensitizers and photoinitiators.

Clinical serum lipidomic profiling revealed potential lipid biomarkers for early diabetic retinopathy.

Diabetic retinopathy (DR) is a serious complication of diabetes featuring abnormal lipid metabolism. However, the specific lipid molecules associated with onset and progression remain unclear. We used a broad-targeted lipidomics approach to assess the lipid changes that occur before the proliferative retinopathy stage and to identify novel lipid biomarkers to distinguish between patients without DR (NDR) and with non-proliferative DR (NPDR). Targeted lipomics analysis was carried out on serum samples from patients with type I diabetes, including 20 NDRs and 20 NPDRs. The results showed that compared with the NDR group, 102 lipids in the NPDR group showed specific expressions. Four lipid metabolites including TAG58:2-FA18:1 were obtained using the Least Absolute Shrink And Selection Operator (LASSO) and Support Vector Machine Recursive Feature Elimination (SVM-RFE) methods. The four-lipid combination diagnostic models showed good predictive ability in both the discovery and validation sets, and were able to distinguish between NDR patients and NPDR patients. The identified lipid markers significantly improved diagnostic accuracy within the NPDR group. Our findings help to better understand the complexity and individual differences of DR lipid metabolism.

Development and validation of a nomogram model of depression and sleep disorders and the risk of disease progression in patients with breast cancer.

BACKGROUND: In this study, we investigated the relationship between the risk of postoperative progressive disease (PD) in breast cancer and depression and sleep disorders in order to develop and validate a suitable risk prevention model. METHODS: A total of 750 postoperative patients with breast cancer were selected from the First People's Hospital of LianYunGang, and the indices of two groups (an event group and a non-event group) were compared to develop and validate a risk prediction model. The relationship between depression, sleep disorders, and PD events was investigated using the follow-up data of the 750 patients. RESULTS: SAS, SDS, and AIS scores differed in the group of patients who experienced postoperative disease progression versus those who did not; the differences were statistically significant and the ability to differentiate prognosis was high. The area under the receiver operating characteristic (ROC) curves (AUC) were: 0.8049 (0.7685-0.8613), 0.768 (0.727-0.809), and 0.7661 (0.724--0.808), with cut-off values of 43.5, 48.5, and 4.5, respectively. Significant variables were screened by single-factor analysis and multi-factor analysis to create model 1, by lasso regression and cross-lasso regression analysis to create model 2, by random forest calculation method to create model 3, by stepwise regression method (backward method) to create model 4, and by including all variables for Cox regression to include significant variables to create model 5. The AUC of model 2 was 0.883 (0.848-0.918) and 0.937 (0.893-0.981) in the training set and validation set, respectively. The clinical efficacy of the model was evaluated using decision curve analysis and clinical impact curve, and then the model 2 variables were transformed into scores, which were validated in two datasets, the training and validation sets, with AUCs of 0.884 (0.848-0.919) and 0.885 (0.818-0.951), respectively. CONCLUSION: We established and verified a model including SAS, SDS and AIS to predict the prognosis of breast cancer patients, and simplified it by scoring, making it convenient for clinical use, providing a theoretical basis for precise intervention in these patients. However, further research is needed to verify the generalization ability of our model.

Acoustic Skyrmionic Mode Coupling and Transferring in a Chain of Subwavelength Metastructures.

Skyrmions, a stable topological vectorial textures characteristic with skyrmionic number, hold promise for advanced applications in information storage and transmission. While the dynamic motion control of skyrmions has been realized with various techniques in magnetics and optics, the manipulation of acoustic skyrmion has not been done. Here, the propagation and control of acoustic skyrmion along a chain of metastructures are shown. In coupled acoustic resonators made with Archimedes spiral channel, the skyrmion hybridization is found giving rise to bonding and antibonding skyrmionic modes. Furthermore, it is experimentally observed that the skyrmionic mode of acoustic velocity field distribution can be robustly transferred covering a long distance and almost no distortion of the skyrmion textures in a chain of metastructures, even if a structure defect is introduced in the travel path. The proposed localized acoustic skyrmionic mode coupling and propagating is expected in future applications for manipulating acoustic information storage and transfer.

Reactive oxygen species/glutathione dual sensitive nanoparticles with encapsulation of miR155 and curcumin for synergized cancer immunotherapy.

Considerable attention has been directed towards exploring the potential efficacy of miR-155 in the realm of cancer immunotherapy. Elevated levels of miR-155 in dendritic cells (DCs) have been shown to enhance their maturation, migration, cytokine secretion, and their ability to promote T cell activation. In addition, overexpression of mir155 in M2 macrophages boost the polarization towards the M1 phenotype. Conversely, miR-155 has the propensity to induce the accumulation of immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor tissue. To account for this discrepancy, it is imperative to get help from a drug that could deal with immunosuppressive effect. Curcumin (CUR) exhibits the capacity to prompt Tregs converse into T helper 1 cells, fostering the polarization of M2 tumor-associated macrophage towards the M1 phenotype, and impeding the recruitment and aggregation of MDSCs within the tumor microenvironment. Nonetheless, CUR is known to exert an immunosuppressive impact on DCs by hindering the expression of maturation markers, cytokines, and chemokines, thereby prevent DCs response to immunostimulatory agents. Hence, a reactive oxygen species/glutathione dual responsive drug conveyance platform (CUR/miR155@DssD-Hb NPs) was devised to co-deliver CUR and miR155, with the aim of exploring their synergistic potential in bolstering a sustained and robust anti-tumor immune response. In vitro and in vivo results have suggested that CUR/miR155@DssD-Hb NPs can effectively inhibit the viability of 4T1 and B16F10 tumor cells, trigger the release of damage associated molecular patterns, stimulate DCs maturation, subsequent activation of CD8+ T cells, diminish immunosuppressive cell populations (MDSCs, Tregs, M2 TAMs and exhausted T cells), promote the formation of long-term immunity and lessen the formation of metastatic nodules in the lungs. In summary, the co-delivery system integrating CUR and miR155 (CUR/miR155@DssD-Hb NPs) demonstrates promise as a promising strategy for the immunotherapy of melanoma and triple negative breast cancer.

TMSOTf-Catalyzed C2-Sulfenylation of Indole Alkaloids Using N-Sulfenylsuccinimides: An Approach for the Total Synthesis of Isatindigotindolosides.

A TMSOTf-catalyzed C2-sulfenylation of indole alkaloids with N-sulfenylsuccinimides has been developed. This straightforward, metal-free, and cost-effective catalytic system produces valuable 2-thioindole derivatives with yields ranging from moderate to excellent. The synthetic applicability demonstrated includes the total syntheses of isatindigotindolosides I-IV.

Gold Nanocluster: A Photoelectric Converter for X-Ray-Activated Chemotherapy.

Despite the promise of activatable chemotherapy, the development of a spatiotemporally controllable strategy for prodrug activation in deep tissues remains challenging. Herein, a proof-of-concept is proposed for a gold nanocluster-based strategy that utilizes X-ray irradiation to trigger the liberation of platinum (Pt)-based prodrug conjugates, thus enabling radiotherapy-directed chemotherapy. Mechanistically, the irradiated activation of prodrugs is achieved through direct photoelectron transfer from the excited-state gold nanoclusters to the Pt(IV) center, resulting in the release of cytotoxic Pt(II) agents. Compared to the traditional combination of chemotherapy and radiotherapy, this radiotherapy-directed chemotherapy strategy offers superior antitumor efficacy and safety benefits through spatiotemporal synergy at the tumor site. Additionally, this strategy elicits robust immunogenic cell death and yields profound outcomes for combined immunotherapy of breast cancer. This versatile strategy is ushering in a new era of radiation-mediated chemistry for controlled drug delivery and the precise regulation of biological processes.

ZO-1 and IL-1RAP Phosphorylation: Potential Role in Mediated Brain-Gut Axis Dysregulation in Irritable Bowel Syndrome-like Stressed Mice.

Background and Objectives: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder often exacerbated by stress, influencing the brain-gut axis (BGA). BGA dysregulation, disrupted intestinal barrier function, altered visceral sensitivity and immune imbalance defects underlying IBS pathogenesis have been emphasized in recent investigations. Phosphoproteomics reveals unique phosphorylation details resulting from environmental stress. Here, we employ phosphoproteomics to explore the molecular mechanisms underlying IBS-like symptoms, mainly focusing on the role of ZO-1 and IL-1RAP phosphorylation. Materials and Methods: Morris water maze (MWM) was used to evaluate memory function for single prolonged stress (SPS). To assess visceral hypersensitivity of IBS-like symptoms, use the Abdominal withdrawal reflex (AWR). Colonic bead expulsion and defecation were used to determine fecal characteristics of the IBS-like symptoms. Then, we applied a phosphoproteomic approach to BGA research to discover the molecular mechanisms underlying the process of visceral hypersensitivity in IBS-like mice following SPS. ZO-1, p-S179-ZO1, IL-1RAP, p-S566-IL-1RAP and GFAP levels in BGA were measured by western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay to validate phosphorylation quantification. Fluorescein isothiocyanate-dextran 4000 and electron-microscopy were performed to observe the structure and function of the intestinal epithelial barrier. Results: The SPS group showed changes in learning and memory ability. SPS exposure affects visceral hypersensitivity, increased fecal water content, and significant diarrheal symptoms. Phosphoproteomic analysis displayed that p-S179-ZO1 and p-S566-IL-1RAP were significantly differentially expressed following SPS. In addition, p-S179-ZO1 was reduced in mice's DRG, colon, small intestine, spinal and hippocampus and intestinal epithelial permeability was increased. GFAP, IL-1ß and p-S566-IL-1RAP were also increased at the same levels in the BGA. And IL-1ß showed no significant difference was observed in serum. Our findings reveal substantial alterations in ZO-1 and IL-1RAP phosphorylation, correlating with increased epithelial permeability and immune imbalance. Conclusions: Overall, decreased p-S179-ZO1 and increased p-S566-IL-1RAP on the BGA result in changes to tight junction structure, compromising the structure and function of the intestinal epithelial barrier and exacerbating immune imbalance in IBS-like stressed mice.

Clearly fluorescent delineating ER+ breast tumor incisal edge and identifying tiny metastatic tumor foci at high resolution.

Fluorescence-image guided surgery (FGS) can intraoperatively provide real-time visualization of a tumor incisal edge and high-resolution identification of tumor foci to improve treatment outcomes. In this contribution, we report a fluorescent probe NB-TAM based on intramolecularly folded photoinduced electron transfer (PET), which displayed a prominent turn-on response in the near-infrared (NIR) window upon specific interaction with the estrogen receptor (ER). Significantly, NB-TAM could delineate a clear tumor incisal edge (tumor-to-normal tissue ratio > 5) in a 70-min time window, and was successfully used to guide the facile and precise resection of ER+ breast tumors in mice. To our surprise, NB-TAM was found to be capable of identifying very tiny lung metastatic ER+ breast tumor foci (0.4 × 0.3 mm), and this ultrahigh resolution was essential to effectively promote tumor resection precision and early diagnosis of tiny tumors. These results clearly elucidate the promising application of NB-TAM as a diagnostic agent for intraoperative fluorescence imaging of ER+ breast cancer.

Ferroptosis-inducing photosensitizers alleviate hypoxia tumor microenvironment for enhanced fluorescence imaging-guided photodynamic therapy.

This study describes H2O2-activated photosensitizer nanoparticles (ICyHD NPs), which inhibit histone deacetylase via binding Zn2+ to induce ferroptosis and upregulate the intracellular O2, thus resulting in enhanced photodynamic therapeutic effect. ICyHD NPs exert strong antitumor effects on mice and have improved the therapeutic precision via observing the increase in cellular fluorescence.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

N-Phenyl-2-Pyridone-Derived Endoperoxide Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis Progression by Three-Pronged Action.

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone, thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of HIF-1α protein, but also inhibits the TGF-ß1 induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in conventional PDT. Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases.

γ-Tocotrienol enhances autophagy of gastric cancer cells by the regulation of GSK3ß/ß-Catenin pathway.

γ-Tocotrienol (γ-T3) is a major subtype of vitamin E, mainly extracted from palm trees, barley, walnuts, and other plants. γ-T3 has effects on anti-inflammation, anti-oxidation, and potential chemoprevention against malignancies. It is still uncompleted to understand the effect of γ-T3 on the inhibitory mechanism of cancer. This study aimed to investigate whether γ-T3 enhanced autophagy in gastric cancer and the underlying molecular mechanism. The results showed that γ-T3 (0-90 µmol/L) inhibited the proliferation of gastric cancer MKN45 cells and AGS cells, and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Autophagy was increased in MKN45 cells treated with γ-T3 (0-45 µmol/L), especially at a dose of 30 µmol/L for 24 h. These effects were reversed by 3-methyladenine pretreatment. Furthermore, γ-T3 (30 µmol/L) also significantly downregulated the expression of pGSK-3ß (ser9) and ß-catenin protein in MKN45 cells, and γ-T3 (20 mg/kg b.w.) effectively decreased the growth of MKN45 cell xenografts in BABL/c mice. GSK-3ß inhibitor-CHIR-99021 reversed the negative regulation of GSK-3ß/ß-Catenin signaling and autophagy. Our findings indicated that γ-T3 enhances autophagy in gastric cancer cells mediated by GSK-3ß/ß-Catenin signaling, which provides new insights into the role of γ-T3 enhancing autophagy in gastric cancer.

KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.

Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Biodegradable Hydrogenated Dimer Acid-Based Plasticizers for PLA with Excellent Plasticization, Thermal Stability and Gas Resistance.

The use of vegetable oil-dervied plasticizers to enhance the flexibility of polylactic acid (PLA) has received much attention due to their renewability, inexpensiveness and biodegradation. However, the double bonds in vegetable oil-based plasticizers limit their compatibility with PLA, resulting in PLA-derived products with reduced flexibility. Herein, we examined soybean oil-derived hydrogenated dimer acid-based polyethylene glycol methyl ether esters (HDA-2n, 2n = 2, 4, 6 or 8, referring to the ethoxy units) developed via the direct esterification of saturated hydrogenated dimer acid and polyethylene glycol monomethyl ethers. The resulting HDA-2n was first used as a plasticizer for PLA, and the effects of the ethoxy units in HDA-2n on the overall performance of the plasticized PLA were systematically investigated. The results showed that, compared with PLA blended with dioctyl terephthalate (DOTP), the PLA plasticized by HDA-8 with the maximum number of ethoxy units (PLA/HDA-8) exhibited better low-temperature resistance (40.1 °C vs. 15.3 °C), thermal stability (246.8 °C vs. 327.6 °C) and gas barrier properties. Additionally, the biodegradation results showed that HDA-8 could be biodegraded by directly burying it in soil. All results suggest that HDA-8 could be used as green alternative to the traditional petroleum-based plasticizer DOTP, which is applied in the PLA industry.

Constructing high axiality mononuclear dysprosium molecular magnets via a regulation-of-co-ligands strategy.

Two lanthanide complexes with formulae [DyIII(LN5)(pentafluoro-PhO)3] (1) and [DyIII(LN5)(2,6-difluoro-PhO)2](BPh4) (2) (LN5 = 2,14-dimethyl-3,6,10,13,19-pentaazabicyclo[13.3.1]nonadecal (19),2,13,15,17-pentaene) were structurally and magnetically characterized. DyIII ions lie in the cavity of a five coordinate nitrogen macrocycle, and in combination with the introduction of multi-fluorinated monodentate phenoxyl coligands a high axiality coordination symmetry is built. Using the pentafluorophenol co-ligand, complex 1 with a D2d coordination environment, is obtained and displays moderate single-molecule magnets (SMMs) behavior. When difluorophenol co-ligands were used, a higher local axisymmetric pentagonal bipyramidal coordination geometry was observed in complex 2, which displays apparent slow magnetic relaxation behavior with a hysteresis temperature of up to 5 K. Further magnetic studies of diluted samples combined with ab initio calculations indicate that the high axiality plays a crucial role in suppressing quantum tunneling of magnetization (QTM) and consequently results in good slow magnetic relaxation behavior. Different fluoro-substituted phenoxyl co-ligands have phenoloxy oxygen atoms with different electrostatic potentials as well as a different number of phenoloxy coligands along the magnetic axis, resulting in different ligand field strengths and coordination symmetries.

Urinary α 1-microglobulin and ß 2-microglobulin as markers of early kidney injury in HIV-positive male patients on tenofovir-based antiretroviral therapy.

BACKGROUND: A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and ß2-microglobulin (ß2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury. METHOD: One hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and ß2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and ß2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and ß 2-microglobulin expression in renal injury. RESULTS: Up to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and ß2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and ß2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and ß2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and ß2MG, respectively. CONCLUSION: The expression level of urinary α1MG and ß2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.