Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.

BACKGROUND: Hepatectomy is the first choice for treating liver cancer. However, inflammatory factors, released in response to pain stimulation, may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies. AIM: To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function. METHODS: Clinical data from patients with liver cancer admitted to Suzhou Ninth People's Hospital from January 2020 to December 2023 were retrospectively analyzed. Thirty-five patients underwent laparoscopic hepatectomy for liver cancer (liver cancer resection group) and 35 patients underwent medical image-guided microwave ablation (liver cancer ablation group). The short-term efficacy, complications, liver function, and immune function indices before and after treatment were compared between the two groups. RESULTS: One month after treatment, 19 patients experienced complete remission (CR), 8 patients experienced partial remission (PR), 6 patients experienced stable disease (SD), and 2 patients experienced disease progression (PD) in the liver cancer resection group. In the liver cancer ablation group, 21 patients experienced CR, 9 patients experienced PR, 3 patients experienced SD, and 2 patients experienced PD. No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups (P > 0.05). After treatment, total bilirubin (41.24 ± 7.35 vs 49.18 ± 8.64 µmol/L, P < 0.001), alanine aminotransferase (30.85 ± 6.23 vs 42.32 ± 7.56 U/L, P < 0.001), CD4+ (43.95 ± 5.72 vs 35.27 ± 5.56, P < 0.001), CD8+ (20.38 ± 3.91 vs 22.75 ± 4.62, P < 0.001), and CD4+/CD8+ (2.16 ± 0.39 vs 1.55 ± 0.32, P < 0.001) were significantly different between the liver cancer ablation and liver cancer resection groups. CONCLUSION: The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar, but liver function recovers quickly after microwave ablation, and microwave ablation may enhance immune function.

Stepwise Synthesis of Low-Symmetry Hexacationic Pyridinium Organic Cages.

An efficient approach was developed for the synthesis of the well-known BlueCage by pre-bridging two 2,4,6-tris(4-pyridyl)-1,3,5-triazine (TPT) panels with one linker followed by cage formation in a much improved yield and shortened reaction time. Such a stepwise methodology was further applied to synthesize three new pyridinium organic cages, C2, C3, and C4, where the low-symmetry cages C3 and C4 with angled panels demonstrated better recognition properties toward 1,1'-bi-2-naphthol (BINOL) than the high-symmetry analogue C2 featuring parallel platforms.

Causal relationship between gut microbiota and differentiated thyroid cancer: a two-sample Mendelian randomization study.

Background: The gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored. Methods: Genome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings. Results: Four bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333-51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333-51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033-10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096-7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148-0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125-0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020-0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037-0.769, p = 0.021). Conclusion: These findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC.

Novel molecular typing reveals the risk of recurrence in patients with early-stage papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is an indolent disease with a favorable prognosis but characterized by a high recurrence rate. We aimed to improve precise stratification of recurrence risk in PTC patients with early stage using multi-gene signatures. PATIENTS AND METHODS: The present study was performed using data from The Cancer Genome Atlas (TCGA) and multi-center datasets. Unsupervised consensus clustering was used to obtain the optimal molecular subtypes and least absolute shrinkage and selection operator (LASSO) analysis was performed to identify potential genes for the construction of recurrence signature. Kaplan-Meier survival analysis and the log-rank test was used to detect survival differences. Harrells concordance index (C-index) was used to assess the performance of the DNA damage repair (DDR) recurrence signature. RESULTS: Through screening 8 candidate gene sets, the entire cohort was successfully stratified into two recurrence-related molecular subtypes based on DDR genes: DDR-high subtype and DDR-low subtype. The recurrence rate of DDR-high subtype was significantly lower than DDR-low subtype [HR = 0.288 (95%CI, 0.084-0.986), P = 0.047]. Further, a two-gene DDR recurrence signature was constructed, including PER1 and EME2. The high-risk group showed a significantly worse recurrence-free survival (RFS) than the low-risk group [HR = 10.647 (95%CI, 1.363-83.197), P = 0.024]. The multi-center data demonstrated that proportion of patients with low expression of PER1 and EME2 was higher in the recurrence group than those in the non-recurrence group. CONCLUSIONS: These findings could help accurately and reliably identify PTC patients with high risk of recurrence so that they could receive more radical and aggressive treatment strategies and more rigorous surveillance practices.

Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis.

Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR-378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR-378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.

Subtle adjustments for constructing multi-nuclear luminescent lanthanide organic polyhedra with triazole-based chelates.

Controlled self-assembly of predetermined multi-nuclear lanthanide organic polyhedra (LOPs) still presents a challenge, primarily due to the unpredictable coordination numbers and labile coordination geometries of lanthanide ions. In this study, through introducing triazole-based chelates to increase the chelating angle of C2-symmetric linear ligands and stabilize the coordination geometry of Eu(III) centers, M4L6-type (M = EuIII, L = ligand) tetrahedra were efficiently synthesized, especially a biphenyl-bridged ligand which is well known to form M2L3-type helicates. A series of LOPs were formed and characterized by high-resolution electrospray ionization time-of-flight mass spectroscopy (ESI-TOF-MS) and X-ray crystallography. Moreover, the europium complexes exhibit bright emission (luminescence quantum yield up to 42.4%) and circularly polarized luminescence properties (|glum| up to 4.5 × 10-2). This study provides a feasible strategy for constructing multi-nuclear luminescent LOPs towards potential applications.

Causal associations between gut microbiota with intervertebral disk degeneration, low back pain, and sciatica: a Mendelian randomization study.

PURPOSE: Although studies have suggested that gut microbiota may be associated with intervertebral disk disease, their causal relationship is unclear. This study aimed to investigate the causal relationship between the gut microbiota and its metabolic pathways with the risk of intervertebral disk degeneration (IVDD), low back pain (LBP), and sciatica. METHODS: Genetic variation data for 211 gut microbiota taxa at the phylum to genus level were obtained from the MiBioGen consortium. Genetic variation data for 105 taxa at the species level and 205 metabolic pathways were obtained from the Dutch Microbiome Project. Genetic variation data for disease outcomes were obtained from the FinnGen consortium. The causal relationships between the gut microbiota and its metabolic pathways and the risk of IVDD, LBP, and sciatica were evaluated via Mendelian randomization (MR). The robustness of the results was assessed through sensitivity analysis. RESULTS: Inverse variance weighting identified 46 taxa and 33 metabolic pathways that were causally related to IVDD, LBP, and sciatica. After correction by weighted median and MR-PRESSO, 15 taxa and nine pathways remained stable. After FDR correction, only the effect of the genus_Eubacterium coprostanoligenes group on IVDD remained stable. Sensitivity analyses showed no evidence of horizontal pleiotropy, heterogeneity, or reverse causation. CONCLUSION: Some microbial taxa and their metabolic pathways are causally related to IVDD, LBP, and sciatica and may serve as potential intervention targets. This study provides new insights into the mechanisms of gut microbiota-mediated development of intervertebral disk disease.

Probability of outbreaks and cross-border dissemination of the emerging pathogen: a genomic survey of Elizabethkingia meningoseptica.

IMPORTANCE: Elizabethkingia meningoseptica is an emerging infectious agent associated with life-threatening infections in immunocompromised individuals. However, there are limited data available on the genomic features of E. meningoseptica. This study aims to characterize the geographical distribution, phylogenetic evolution, pathogenesis, and transmission of this bacterium. A systematic analysis of the E. meningoseptica genome revealed that a common ancestor of this bacterium existed 90 years ago. The evolutionary history showed no significant relationship with the sample source, origin, or region, despite the presence of genetic diversity. Whole genome sequencing data also demonstrated that E. meningoseptica bacteria possess inherent resistance and pathogenicity, enabling them to spread within the same hospital and even across borders. This study highlights the potential for E. meningoseptica to cause severe nosocomial outbreaks and horizontal transmission between countries worldwide. The available evidence is crucial for the development of evidence-based public health policies to prevent global outbreaks caused by emerging pathogens.

Excited-Multimer Mediated Supramolecular Upconversion on Multicomponent Lanthanide-Organic Assemblies.

Upconversion (UC) is a fascinating anti-Stokes-like optical process with promising applications in diverse fields. However, known UC mechanisms are mainly based on direct energy transfer between metal ions, which constrains the designability and tunability of the structures and properties. Here, we synthesize two types of Ln8L12-type (Ln for lanthanide ion; L for organic ligand L1 or L2R/S) lanthanide-organic complexes with assembly induced excited-multimer states. The Yb8(L2R/S)12 assembly exhibits upconverted multimer green fluorescence under 980 nm excitation through a cooperative sensitization process. Furthermore, upconverted red emission from Eu3+ on the heterometallic (Yb/Eu)8L12 assemblies is also realized via excited-multimer mediated energy relay. Our findings demonstrate a new strategy for designing UC materials, which is crucial for exploiting photofunctions of multicomponent lanthanide-organic complexes.

Counteranion-mediated efficient iodine capture in a hexacationic imidazolium organic cage enabled by multiple non-covalent interactions.

Developing efficient adsorbents to capture radioactive iodine produced from nuclear wastes is highly desired. Here we report the facial synthesis of a hexacationic imidazolium organic cage and its iodine adsorption properties. Crucial role of counteranions has been disclosed for iodine capture with this cage, where distinct iodine capture behaviors were observed when different counteranions were used. Mechanistic investigations, especially with the X-ray crystallographic analysis of the iodine-loaded sample, allowed the direct visualization of the iodine binding modes at the molecular level. A network of multiple non-covalent interactions including hydrogen bonds, halogen bonds, anion···π interactions, electrostatic interaction between polyiodides and the hexacationic skeleton of the cage are found responsible for the observed high iodine capture performance. Our results may provide an alternative strategy to design efficient iodine adsorbents.

Controlled Self-Assembly, Isomerism, and Guest Uptake/Release of Charge-Reversible Lanthanide-Organic Octahedral Cages.

Charge plays a crucial role in the function of molecular and supramolecular systems, but coordination hosts capable of orthogonal charge regulation remain elusive so far. In this study, we report the condition-dependent self-assembly of charge-reversible lanthanide-organic tetra-capped octahedral cages, i.e., [Ln6(H3L)4]6+ and [Ln6L4]6-, from a series of lanthanide ions (Ln3+; Ln = Lu, Yb, Eu) and a tritopic tetradentate acylhydrazone ligand (H6L) featuring multiple deprotonation states and propeller conformations. While direct self-assembly under basic conditions produced a mixture of various ΔxΛ6-x-[Ln6L4]6- (x = 0-6) stereoisomers, racemic Δ6- and Λ6-[Ln6L4]6- could be exclusively obtained from the first self-assembly of Δ6- and Λ6-[Ln6(H3L)4]6+ under neutral conditions followed by post-assembly deprotonation. Rich isomerism on the tetra-capped octahedral cages arising from the coupling between the metal-centered Δ/Λ chirality and the ligand conformations has been discussed based on X-ray single-crystal structures of the C3-symmetric Δ3Λ3-Ln6L4 and T-symmetric Δ6/Λ6-Ln6L4 complexes. Host-guest studies confirmed that positively charged rac-Δ6/Λ6-[Ln6(H3L)4]6+ could bind anionic sulfonates, and negatively charged rac-Δ6/Λ6-[Ln6L4]6- exhibited strong encapsulation ability toward ammonium guests, where acid/base-triggered guest uptake/release could be realized taking advantage of the charge reversibility of the cage. Moreover, photophysical studies revealed visible-light-sensitized and guest-encapsulation-enhanced NIR emissions on the rac-Δ6/Λ6-Yb6L4 cage. This work not only enriches the library of functional lanthanide-organic cages but also provides a promising candidate with charge reversibility for the development of smart supramolecular materials.

A Pd4L2 cage containing Brønsted-base active sites for the one-pot photooxidation/Knoevenagel condensation reaction.

Brønsted-base active sites on a Pd4L2 cage facilitates enhanced catalytic efficiency, wide substrate scope and high turnover number (TON) for the one-pot photooxidation/Knoevenagel condensation reaction under mild conditions.

Dynamic Interconversion and Induced-Fit Guest Binding with Two Macrocycle-Based Coordination Cages.

We report the syntheses and host-guest chemistry of two interconvertible coordination cages, Pd2L2 and Pd1L1, from a dynamic macrocycle ligand (L) and a cis-blocking (tmen)Pd(NO3)2 (tmen = tetramethylethylenediamine) unit (Pd). The water-soluble macrocyclic L, which can bind various polycyclic aromatic hydrocarbon (PAH) guests in its cis-conformation, was constructed via four pyridinium bonds between two 2,4,6-tri(4-pyridyl)-1,3,5-triazine [TPT] panels and two p-xylene bridges. We selectively formed each cage either by changing the reaction concentration/solvent/temperature or through induced-fit guest encapsulation, while direct assembly of L and Pd resulted in a mixture of Pd2L2 and Pd1L1 in equilibrium. X-ray structures of the free ligand and the host-guest complexes confirmed the induce-fit adaptive changes in the ligand's conformation and the cage's cavity. This work demonstrates a useful strategy for designing multistimuli-responsive supramolecular hosts by coordination self-assembly with macrocyclic ligands featuring rich conformational freedom.

Retinoic acid inhibits the pyroptosis of degenerated nucleus pulposus cells by activating Sirt1-SOD2 signaling.

AIM: Intervertebral disc (IVD) degeneration is a common disease initiated by the degeneration of the nucleus pulposus (NP). The pyroptosis of degenerated NP cells (dNPCs) plays an important role in NP degeneration. The purpose of this study is to identify a feasible solution that can inhibit NP cell pyroptosis to therapy the degeneration of the intervertebral disc. METHODS: Cell viability and proliferation were quantified by Cell Counting Kit-8 assay. The measurement of cellular reactive oxygen species (ROS) was detected by 2,7-Dichlorodi-hydrofluorescein diacetate. The death of cells was analyzed by the Terminal Deoxynucleotidyl Transferase-mediated dUTP Nick-End Labeling (TUNEL) method of fluorescence analysis. The pyroptosis of cells was assessed by flow cytometry analyses. The contents of sulfate glycosaminoglycans were detected by a blyscan assay kit. RESULT: In this study, we determined the effects of retinoic acid (RA) on dNPCs and investigated the underlying mechanism of RA-mediated pyroptosis in dNPCs. We also verified the effects of RA on IVD degeneration in vivo. Our results demonstrated that RA significantly increased the proliferation and the protein expression of sox9, aggrecan, and collagen II of dNPCs. Pyroptosis-related proteins and the pyroptosis rate of dNPCs were significantly decreased by RA. We found that Sirt1-SOD2 signaling was activated, while ROS generation and TXNIP/NLRP3 signaling in dNPCs were inhibited after the addition of RA. Furthermore, RA also recovered the structure of NP and increased the contents of sulfated glycosaminoglycans and collagen in vivo. CONCLUSION: Our study demonstrated that RA could inhibit the pyroptosis and increase the extracellular matrix synthesis function of dNPCs and verified that RA has a protective effect on IVD degeneration.

Neighbor Reweighted Local Centroid for Geometric Feature Identification.

Identifying geometric features from sampled surfaces is a significant and fundamental task. The existing curvature-based methods that can identify ridge and valley features are generally sensitive to noise. Without requiring high-order differential operators, most statistics-based methods sacrifice certain extents of the feature descriptive powers in exchange for robustness. However, neither of these types of methods can treat the surface boundary features simultaneously. In this paper, we propose a novel neighbor reweighted local centroid (NRLC) computational algorithm to identify geometric features for point cloud models. It constructs a feature descriptor for the considered point via decomposing each of its neighboring vectors into two orthogonal directions. A neighboring vector starts from the considered point and ends with the corresponding neighbor. The decomposed neighboring vectors are then accumulated with different weights to generate the NRLC. With the defined NRLC, we design a probability set for each candidate feature point so that the convex, concave and surface boundary points can be recognized concurrently. In addition, we introduce a pair of feature operators, including assimilation and dissimilation, to further strengthen the identified geometric features. Finally, we test NRLC on a large body of point cloud models derived from different data sources. Several groups of the comparison experiments are conducted, and the results verify the validity and efficiency of our NRLC method.

Dinuclear mono-bridged or polymeric lanthanide complexes from one ligand: structural transformation and chiral induction.

We designed and synthesized a semi-rigid bis-tridentate ligand L which could undergo a trans-to-cis conformational transition when coordinated onto lanthanum ions through the rotation of the single bond on the central terphenyl bridge. By adjusting the metal/ligand ratio, a single-ligand bridged dinuclear complex La2L3 and an infinitely extending two-dimensional layered metal organic polymer (La2L2)n can be obtained. Through the induction of the chiral auxiliary ligand GR/S, these two achiral assemblies could both be transformed into the chiral mononuclear three-component complex LaLGR/S. In addition, we also realized a linear ee sensing for the auxiliary ligand by induced circular dichroism.

Corrigendum: Lobectomy may be more appropriate for patients with early-stage medullary thyroid cancer older than 60 years old.

[This corrects the article DOI: 10.3389/fendo.2022.1015319.].

Lobectomy may be more appropriate for patients with early-stage medullary thyroid cancer older than 60 years old.

Purpose: Clinical guidelines presently recommend total thyroidectomy for the treatment of medullary thyroid cancer (MTC). This study was aimed to investigate whether lobectomy could be the initial treatment for stage I MTC patients. Methods: The retrospective study was based on data from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The risk factors of survival were estimated by the univariate and multivariate Cox proportional-hazards model. The effect of age on death risk was estimated using restricted cubic splines. Survival curves were constructed according to the Kaplan-Meier method. Results: A total of 988 stage I MTC patients was included in the study. Among them, 506 (51.2%) MTC patients received lobectomy and 482 (48.8%) received total thyroidectomy. The only independent prognostic factor for overall survival (OS) and disease-specific survival (DSS) was age, according to univariate and multivariate Cox regression analysis. The hazard ratio (HR) increased relatively slowly with age growing under the age of approximately 60 years. However, the death risk of MTC patients began to rise sharply with increasing age above 60 years. For patients under the age of 60, a significant survival difference for OS and DSS was observed between the lobectomy group and total thyroidectomy group (p < 0.05). However, for patients aged above 60, no significant survival difference was observed for OS or DSS (p > 0.05). Conclusion: Total thyroidectomy was an appropriate treatment for stage I MTC patients under the age of 60, which was consistent with the recommendation of the clinical guidelines. However, for those over the age of 60, lobectomy may be explored as a better surgical option. The findings may provide the evidence base for improving the clinical management of stage I MTC patients. Further prospective multicenter clinical studies are needed including information regarding RET status as well as calcitonin and CEA levels.

Stereocontrolled Self-Assembly of Ln(III)-Pt(II) Heterometallic Cages with Temperature-Dependent Luminescence.

Structurally well-defined discrete d/f heterometallic complexes show diverse application potential in electrooptic and magnetic materials. However, precise control of the component and topology of such heterometallic compounds with fine-tuned photophysical properties is still challenging. Herein, we report the stereocontrolled syntheses of a series of LnIII-PtII heterometallic cages through coordination-driven self-assembly of enantiopure alkynylplatinum-based metalloligands (L1R/S, L2R/S) with lanthanide ions (Ln = EuIII, YbIII, NdIII, LuIII). Taking advantage of the metal-to-ligand charge transfer (MLCT) excited state on the designed alkynylplatinum ligands, the excitation window for the sensitized near-infrared (NIR) luminescence on the YbIII- and NdIII-containing cages can be extended to the visible region (up to 500 nm). Linear temperature-dependent red and NIR emissions observed on the Ln4(L2R/S)6 (LnIII = EuIII and YbIII, respectively) complexes suggest their potential applications as luminescent temperature sensors, with sensitivities of -0.54% (LnIII = EuIII, 77-250 K) and -0.17% (LnIII = YbIII, 77-300 K) per K achieved. This work not only offers a good strategy to prepare new d/f heterometallic supramolecular cages but also paves the way for the design of stimuli-responsive luminescent materials.