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1.
Hear Res ; 450: 109067, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38870778

ABSTRACT

The study aimed to explore the auditory temporal resolution and dichotic listening skills in patients with type 2 diabetes mellitus (T2DM) and identify associated health-related factors. Using a cross-sectional design, 87 adults with T2DM and 48 non-diabetic controls, all with normal hearing, participated. The two central auditory processing (CAP) skills were assessed through the Gaps-In-Noise (GIN) and Dichotic-Digits Listening (DDL) tests. T2DM participants underwent blood tests to measure various health-related factors. In the GIN test, the shortest gap threshold (GapTh) obtained across both ears was significantly higher in the diabetic group (9.1 ± 2.4 ms) compared to the non-diabetic group (7.5 ± 1.5 ms), and the score of correctly identified gaps (GapSc) in the diabetic group (45±11 %) was significantly lower than GapSc in the non-diabetic group (52±9 %), p < 0.001. In the DDL test, the free-recall score (73.8 ± 18.5 %) across both ears and the right-ear advantage (-1.3 ± 20.6 %) in the diabetic group were significantly lower than the free-recall score (85.8 ± 11.9 %) and right-ear advantage (6.9 ± 11.9 %) in the non-diabetic group, p < 0.005. Furthermore, the duration of diabetes, eGFR level, retinopathy, carotid plaque, fasting blood glucose level, and HDL-C (good cholesterol) level were factors significantly associated with performances in the GIN and/or DDL tests for T2DM participants. In conclusion, individuals with T2DM are at risk of reduced auditory processing skills in temporal resolution and dichotic listening, impacting their speech understanding. Six health-related factors were identified as significantly associated with CAP skills in T2DM patients.

2.
Adv Sci (Weinh) ; : e2402255, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38885363

ABSTRACT

In this study, a novel approach for the tertiary α-alkylation of ketones using alkanes with electron-deficient C─H bonds is presented, employing a synergistic catalytic system combining inexpensive copper salts with aminocatalysis. This methodology addresses the limitations of traditional alkylation methods, such as the need for strong metallic bases, regioselectivity issues, and the risk of over alkylation, by providing a high reactivity and chemoselectivity without the necessity for pre-functionalized substrates. The dual catalytic strategy enables the direct functionalization of C(sp3)─H bonds, demonstrating remarkable selectivity in the presence of conventional C(sp3)─H bonds that are adjacent to heteroatoms or π systems, which are typically susceptible to single-electron transfer processes. The findings contribute to the advancement of alkylation techniques, offering a practical and efficient route for the construction of C(sp3)─C(sp3) bonds, and paving the way for further developments in the synthesis of complex organic molecules.

3.
Plants (Basel) ; 13(10)2024 May 07.
Article in English | MEDLINE | ID: mdl-38794357

ABSTRACT

The SAUR (small auxin-up RNA) family constitutes a category of genes that promptly respond to the hormone auxin and play a pivotal role in diverse biological processes encompassing plant growth and the response to abiotic stress. Santalum album L., a semi-parasitic evergreen tree, is renowned for its economically valuable essential oils, positioning it among the most prized tree species. In this study, a meticulous identification and comprehensive analysis of 43 SAUR genes was conducted within S. album. Based on phylogenetic relationships, the SaSAUR genes were systematically categorized into five groups. A collinearity analysis revealed intriguing insights, disclosing 14 segmental duplications and 9 tandem duplications within the SaSAUR genes, emphasizing the pivotal role of duplication in the expansion of this gene family. Noteworthy variations in the expression levels of SaSAUR genes were observed by delving into the SaSAUR transcriptome data from various tissues, including leaves, roots, and heartwood, as well as under salt-stress conditions. Notably, SaSAUR08 and SaSAUR13 were significantly upregulated in heartwood compared with roots and leaves, while SaSAUR18 was markedly more expressed in roots compared with heartwood and leaves. Furthermore, SaSAUR27 and SaSAUR28 were found to respond closely to salt stress, hinting at their potential involvement in the salt-stress response mechanism. This research offers a comprehensive investigation of SAUR genes in S. album and establishes a foundation for future exploration of the SAUR gene family, particularly its relation to growth and salt-stress responses.

4.
Chem Sci ; 15(19): 7308-7315, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38756792

ABSTRACT

Surface-enhanced Raman scattering (SERS) spectroscopy is an effective technique that can reveal molecular structure and molecular interaction details. Semiconductor-based SERS platforms exhibit multifaceted tunability and unique selectivity to target molecules as well as high spectral reproducibility. However, the detection sensitivity of semiconductors is impeded by inferior SERS enhancement. Herein, a surface and interference co-enhanced Raman scattering (SICERS) platform based on corrugated TiO2 nanotube arrays (c-TiO2 NTs) was developed, and the coupling of structural regulation and photo-induced charge transfer (PICT) effectively optimized the SERS performance of the semiconductor substrate. Due to the regularly oscillating optical properties of the c-TiO2 NTs, well-defined interference patterns were generated and the local electric field was significantly increased, which greatly promoted both the electromagnetic mechanism and PICT processes. The c-TiO2 NTs were subsequently applied as a highly sensitive SICERS substrate to investigate the mechanism of temperature influence on enantioselective identification. This identification process is related to the existence of temperature-sensitive hydrogen bonds and π-π interaction. This work demonstrates a simply prepared, low-cost, and sensitive SERS substrate that enables better investigation into molecular identification.

5.
Mater Today Bio ; 26: 101080, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38757056

ABSTRACT

The unique gradient structure and complex composition of osteochondral tissue pose significant challenges in defect regeneration. Restoration of tissue heterogeneity while maintaining hyaline cartilage components has been a difficulty of an osteochondral tissue graft. A novel class of multi-crosslinked polysaccharide-based three-dimensional (3D) printing inks, including decellularized natural cartilage (dNC) and nano-hydroxyapatite, was designed to create a gradient scaffold with a robust interface-binding force. Herein, we report combining a dual-nozzle cross-printing technology and a gradient crosslinking method to create the scaffolds, demonstrating stable mechanical properties and heterogeneous bilayer structures. Biofunctional assessments revealed the remarkable regenerative effects of the scaffold, manifesting three orders of magnitude of mRNA upregulation during chondrogenesis and the formation of pure hyaline cartilage. Transcriptomics of the regeneration site in vivo and scaffold cell interaction tests in vitro showed that printed porous multilayer scaffolds could form the correct tissue structure for cell migration. More importantly, polysaccharides with dNC provided a hydrophilic microenvironment. The microenvironment is crucial in osteochondral regeneration because it could guide the regenerated cartilage to ensure the hyaline phenotype.

6.
Bioresour Technol ; 402: 130838, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38740312

ABSTRACT

Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation.


Subject(s)
Bioreactors , Phylogeny , Stochastic Processes , Bioreactors/microbiology , Filtration , Sewage/microbiology , Bacteria/metabolism , Bacteria/genetics , Biofilms , Microbiota , RNA, Ribosomal, 16S/genetics
7.
PLoS One ; 19(5): e0303909, 2024.
Article in English | MEDLINE | ID: mdl-38814950

ABSTRACT

The ADAMTS Like 2 (ADAMTSL2) mutation has been identified to be associated with different human genetic diseases. The role of ADAMTSL2 is unclear in colorectal cancer (CRC). The study investigated the expression of ADAMTSL2 in both pan cancer and CRC, using data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The study examined the correlation between ADAMTSL2 expression levels and clinical characteristics, as well as prognosis in CRC. The study explored potential regulatory networks involving ADAMTSL2, including its association with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB) / microsatellite instability (MSI), tumor stemness index (mRNAsi), and drug sensitivity in CRC. ADAMTSL2 expression was validated using GSE71187 and quantitative real-time PCR (qRT-PCR). ADAMTSL2 was aberrantly expressed in pan cancer and CRC. An increased level of ADAMTSL2 expression in patients with CRC was significantly associated with the pathologic N stage (p < 0.001), pathologic stage (p < 0.001), age (p < 0.001), histological type (p < 0.001), and neoplasm type (p = 0.001). The high expression of ADAMTSL2 in patients with CRC was found to be significantly associated with a poorer overall survival (OS) (HR: 1.67; 95% CI: 1.18-2.38; p = 0.004), progression-free survival (PFS) (HR: 1.55; 95% CI: 1.14-2.11; p = 0.005) and disease-specific survival (DSS) (HR: 1.83; 95% CI: 1.16-2.89; p = 0.010). The expression of ADAMTSL2 in patients with CRC (p = 0.009) was identified as an independent prognostic determinant. ADAMTSL2 was associated with extracellular matrix receptor (ECM-receptor) interaction, transforming growth factor ß (TGF-ß) signaling pathway, and more. ADAMTSL2 expression was correlated with immune infiltration, immune checkpoint genes, TMB / MSI and mRNAsi in CRC. ADAMTSL2 expression was significantly and negatively correlated with 1-BET-762, Trametinib, and WZ3105 in CRC. ADAMTSL2 was significantly upregulated in CRC cell lines. The high expression of ADAMTSL2 is significantly correlated with lower OS and immune infiltration of CRC. ADAMTSL2 may be a potential prognostic biomarker and immunotherapeutic target for CRC patients.


Subject(s)
ADAMTS Proteins , Biomarkers, Tumor , Colorectal Neoplasms , Computational Biology , Humans , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , ADAMTS Proteins/genetics , ADAMTS Proteins/metabolism , Computational Biology/methods , Female , Male , Gene Expression Regulation, Neoplastic , Middle Aged , Microsatellite Instability , Aged , Immunotherapy , Cell Line, Tumor
8.
Int Immunopharmacol ; 135: 112290, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38796964

ABSTRACT

Anesthesia and surgery activate matrix metalloproteinase 9 (MMP9), leading to blood-brain barrier (BBB) disruption and postoperative delirium (POD)-like behavior, especially in the elderly. Aged mice received intraperitoneal injections of either the MMP9 inhibitor SB-3CT, melatonin, or solvent, and underwent laparotomy under 3 % sevoflurane anesthesia(anesthesia/surgery). Behavioral tests were performed 24 h pre- and post-operatively. Serum and cortical tissue levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured using ELISA. Levels of PDGFRß, MMP9, tight junction, Mfsd2a, caveolin-1, synaptophysin, and postsynaptic densin (PSD)-95 proteins in the prefrontal cortex were assayed using Western blotting. BBB permeability was assessed by detecting IgG in the prefrontal cortex and serum S100ß levels. Anesthesia/surgery-induced peripheral inflammation activated MMP9, which in turn injured pericytes and tight junctions and increased transcytosis, thereby disrupting the BBB. Impaired BBB allowed the migration of peripheral inflammation into the central nervous system (CNS), thereby inducing neuroinflammation, synaptic dysfunction, and POD-like behaviors. However, MMP9 inhibition reduced pericyte and tight junction injury and transcytosis, thereby preserving BBB function and preventing the migration of peripheral inflammation into the CNS, thus attenuating synaptic dysfunction and POD-like behavior. In addition, to further validate the above findings, we showed that melatonin exerted similar effects through inhibition of MMP9. The present study shows that after anesthesia/surgery, inflammatory cytokines upregulation is involved in regulating BBB permeability in aged mice through activation of MMP9, suggesting that MMP9 may be a potential target for the prevention of POD.


Subject(s)
Blood-Brain Barrier , Matrix Metalloproteinase 9 , Melatonin , Neuroinflammatory Diseases , Sevoflurane , Animals , Matrix Metalloproteinase 9/metabolism , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Male , Mice , Sevoflurane/pharmacology , Neuroinflammatory Diseases/immunology , Melatonin/pharmacology , Aging , Mice, Inbred C57BL , Prefrontal Cortex/metabolism , Prefrontal Cortex/drug effects , Cytokines/metabolism , Postoperative Complications , Anesthesia , Behavior, Animal/drug effects , Laparotomy/adverse effects , Tight Junctions/metabolism , Tight Junctions/drug effects , Heterocyclic Compounds, 1-Ring , Sulfones
9.
Opt Express ; 32(6): 9625-9633, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571192

ABSTRACT

We demonstrate a compact watt-level all polarization-maintaining (PM) femtosecond fiber laser source at 1100 nm. The fiber laser source is seeded by an all PM fiber mode-locked laser employing a nonlinear amplifying loop mirror. The seed laser can generate stable pulses at a fundamental repetition rate of 40.71 MHz with a signal-to-noise rate of >100 dB and an integrated relative intensity noise of only ∼0.061%. After two-stage external amplification and pulse compression, an output power of ∼1.47 W (corresponding to a pulse energy of ∼36.1 nJ) and a pulse duration of ∼251 fs are obtained. The 1100 nm femtosecond fiber laser is then employed as the excitation light source for multicolor multi-photon fluorescence microscopy of Chinese hamster ovary (CHO) cells stably expressing red fluorescent proteins.

10.
World J Urol ; 42(1): 259, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662226

ABSTRACT

PURPOSE: The aim of this study was to explore the benefit the metastasectomy for patients with metastatic non-clear cell carcinoma (non-ccRCC). METHODS: This study enrolled 120 patients with confirmed metastatic non-ccRCC from the RCC database of our center from 2008 to 2021. Patients without metastasectomy were grouped as radical nephrectomy without metastasectomy patients. The clinical outcomes included overall survival (OS) and progression-free survival (PFS). Cox regression and Kaplan-Meier analyses were used to assess potential factors that predict clinical benefits from metastasectomy. RESULTS: A total of 100 patients received radical nephrectomy alone, while the remaining 20 patients underwent both radical nephrectomy and metastasectomy. There was no significant difference in age between the two groups. Out of 100 patients who underwent radical nephrectomy, 60 were male, and out of 20 patients who had both radical nephrectomy and metastasectomy, 12 were male. Patients who underwent systemic therapy plus radical nephrectomy and metastasectomy had significantly better PFS (27.1 vs. 14.0, p = 0.032) and OS (67.3 vs. 24.0, p = 0.043) than those who underwent systemic therapy plus radical nephrectomy alone. Furthermore, for patients without liver metastasis (n = 54), systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.028) and OS (p = 0.043). Similarly, for patients with metachronous metastasis, systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.043) and OS (p = 0.032). None of the patients experienced serious perioperative complications (Clavien-Dindo Classification ≥ III grade). CONCLUSION: Metastasectomy in patients with metastatic non-ccRCC may provide clinical benefits in terms of improved PFS and OS, especially in patients without liver metastasis and those with metachronous metastasis.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Metastasectomy , Nephrectomy , Humans , Male , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/mortality , Female , Retrospective Studies , Middle Aged , Nephrectomy/methods , Survival Rate , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/mortality , Aged , Cohort Studies , Adult
11.
Sci Total Environ ; 927: 172376, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38604376

ABSTRACT

Biofilms are widely used and play important roles in biological processes. Low temperature of wastewater inhibits the development of biofilms derived from wastewater activated sludge. However, the specific mechanism of temperature on biofilm development is still unclear. This study explored the mechanism of temperature on biofilm development and found a feasible method to enhance biofilm development at low temperature. The amount of biofilm development decreased by approximately 66 % and 55 % at 4 °C and 15 °C, respectively, as compared to 28 °C. The cyclic dimeric guanosine monophosphate (c-di-GMP) concentration also decreased at low temperature and was positively correlated with extracellular polymeric substance (EPS) content, formation, and adhesion strength. Microbial community results showed that low temperature inhibited the normal survival of most microorganisms, but promoted the growth of some psychrophile bacteria like Sporosarcina, Caldilineaceae, Gemmataceae, Anaerolineaceae and Acidobacteriota. Further analysis of functional genes demonstrated that the abundance of functional genes related to the synthesis of c-di-GMP (K18968, K18967 and K13590) decreased at low temperature. Subsequently, the addition of exogenous spermidine increased the level of intracellular c-di-GMP and alleviated the inhibition effect of low temperature on biofilm development. Therefore, the possible mechanism of low temperature on biofilm development could be the inhibition of the microorganism activity and reduction of the communication level between cells, which is the closely related to the EPS content, formation, and adhesion strength. The enhancement of c-di-GMP level through the exogenous addition of spermidine provides an alternative strategy to enhance biofilm development at low temperatures. The results of this study enhance the understanding of the influence of temperature on biofilm development and provide possible strategies for enhancing biofilm development at low temperatures.


Subject(s)
Bacteria , Biofilms , Cyclic GMP , Bacterial Physiological Phenomena , Cold Temperature , Cyclic GMP/analogs & derivatives , Cyclic GMP/metabolism , Extracellular Polymeric Substance Matrix , Wastewater/microbiology
12.
Prostate ; 84(10): 932-944, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38629249

ABSTRACT

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.


Subject(s)
Androstenes , Biomarkers, Tumor , Ki-67 Antigen , Prostatic Neoplasms , Humans , Male , Ki-67 Antigen/analysis , Ki-67 Antigen/metabolism , Aged , Androstenes/therapeutic use , Retrospective Studies , Middle Aged , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Cell Proliferation/drug effects , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/metabolism , Treatment Outcome , Predictive Value of Tests , Progression-Free Survival , Aged, 80 and over , Antineoplastic Agents/therapeutic use
13.
Commun Biol ; 7(1): 398, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561482

ABSTRACT

Metabolic reprogramming plays an important role in kidney cancer. We aim to investigate the causal effect of 249 metabolic biomarkers on kidney cancer from population-based data. This study extracts data from previous genome wide association studies with large sample size. The primary endpoint is random-effect inverse variance weighted (IVW). After completing 249 times of two-sample Mendelian randomization analysis, those significant metabolites are included for further sensitivity analysis. According to a strict Bonferrion-corrected level (P < 2e-04), we only find two metabolites that are causally associated with renal cancer. They are lactate (OR:3.25, 95% CI: 1.84-5.76, P = 5.08e-05) and phospholipids to total lipids ratio in large LDL (low density lipoprotein) (OR: 0.63, 95% CI: 0.50-0.80, P = 1.39e-04). The results are stable through all the sensitivity analysis. The results emphasize the central role of lactate in kidney tumorigenesis and provide novel insights into possible mechanism how phospholipids could affect kidney tumorigenesis.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Genome-Wide Association Study , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Carcinogenesis , Lactic Acid , Mendelian Randomization Analysis , Phospholipids , Biomarkers
14.
Surg Innov ; 31(3): 307-317, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38606504

ABSTRACT

BACKGROUND: Reconstructing bone defects in the upper extremities and restoring their functions poses a significant challenge. In this study, we describe a novel workflow for designing and manufacturing customized bone cement molds using 3D printing technology to reconstruct upper extremity defects after bone tumor resection. METHODS: Computer tomography data was acquired from the unaffected upper extremities to create a detachable mold, which can be customized to fit the joint precisely by shaping the bone cement accordingly. Fourteen patients who underwent reconstructive surgery following bone tumor resection in the proximal humerus (13 cases) or distal radius (1 case) between January 2014 and December 2022 were retrospectively evaluated. The medical records of this case series were reviewed for the demographic, radiological, and operative data. Metastasis, local recurrence, and complication were also reviewed. Additionally, Musculoskeletal Tumor Society Score (MSTS) and Visual Analogue Scale (VAS) were used to assess clinical outcomes. RESULTS: The mean follow-up period was 49.36 ± 15.18 months (range, 27-82 months). At the end of follow-up, there were no cases of metastasis or recurrence, and patients did not experience complications such as infection, dislocation, or implant loosening. Two cases complicated with subluxation (14.3%), and 1 case underwent revision surgery for prosthetic fracture (7.1%). The average MSTS score was 23.2 ± 1.76 (77.4%, range, 66.7%-86.7%), and the postoperative VAS score was 1.86 ± 1.03 (range, 1-4), which was significantly lower than that before surgery (average preoperative VAS score was 5.21 ± 2.00 (range, 2-8)) (P < .001). CONCLUSION: Customized 3D molds can be utilized to shape bone cement prostheses, which may serve as a potential alternative for reconstructing the proximal humerus and distal radius following en bloc resection of bone tumors. This reconstruction strategy offers apparent advantages, including precise matching of articular surfaces and comparatively reduced costs.


Subject(s)
Bone Cements , Bone Neoplasms , Plastic Surgery Procedures , Printing, Three-Dimensional , Humans , Bone Cements/therapeutic use , Bone Neoplasms/surgery , Female , Male , Plastic Surgery Procedures/methods , Retrospective Studies , Adult , Middle Aged , Upper Extremity/surgery , Radius/surgery , Young Adult , Humerus/surgery , Adolescent , Aged , Tomography, X-Ray Computed
15.
Clin Cancer Res ; 30(11): 2571-2581, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38512114

ABSTRACT

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis. RESULTS: In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.


Subject(s)
Carcinoma, Renal Cell , Fumarate Hydratase , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/therapy , Fumarate Hydratase/deficiency , Fumarate Hydratase/genetics , Male , Female , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/immunology , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Middle Aged , Aged , Adult , Lymphocyte Activation/immunology , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/adverse effects , Immunologic Memory , Prognosis , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/pharmacology , Immunotherapy/methods , Memory T Cells/immunology , T-Lymphocytes/immunology
16.
Article in English | MEDLINE | ID: mdl-38506573

ABSTRACT

INTRODUCTION: Previous studies have suggested a relationship between bad mood and asthma. Therefore, in this study, a two-sample Mendelian randomization (MR) method was used to explore the correlation between irritability and asthma. MATERIAL AND METHODS: Relevant instrumental variables (IVs) were extracted from the aggregated data of the genome-wide association studies (GWAS) database. Inverse-variance weighting (IVW) and weighted median (WME) were used for the MR analysis to evaluate the causal relationship between irritability and asthma using odds ratios (ORs) and the corresponding 95% confidence intervals (CIs), respectively. The "leave-one-out" method was used for sensitivity analysis. RESULTS: The results of IVW analysis using random-effects models suggested that irritability increased the risk of asthma (OR = 1.954, 95% CI = 1.188-3.214, p = 0.008). The results of WME were consistent with this observation (OR = 1.934, 95% CI = 1.100-3.400, p = 0.021). Additionally, gastroesophageal reflux disease (GERD) might account for approximately 40% of the relationship between irritability and asthma. The sensitivity analysis revealed the stability of the results. CONCLUSION: The causal relationship between irritability and asthma was analyzed through MR analysis. Irritability increased the risk of asthma. GERD might play an important mediating role in this relationship.

17.
Chem Asian J ; 19(9): e202400049, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38450996

ABSTRACT

This paper explores recent advancements in the field of circularly polarized luminescence (CPL) exhibited by small and isolated organic molecules. The development and application of small CPL molecule are systematically reviewed through eight different chiral skeleton sections. Investigating the intricate interplay between molecular structure and CPL properties, the paper aims at providing and enlighting novel strategies for CPL-based applications.

18.
Int Urol Nephrol ; 56(6): 1859-1868, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38300449

ABSTRACT

INTRODUCTION AND OBJECTIVE: Diabetes mellitus (DM), one of the most common comorbidities in patients with renal cell carcinoma (RCC), was proven to be an important prognostic factor of overall survival for these patients. Regarding the influence on renal function after nephrectomy, evidence is still scant. This systematic review and meta-analysis was conducted to provide a more reliable analysis of the association between DM and long-term renal functional outcomes after nephrectomy. METHODS: The PubMed, Web of Science, Embase and Cochrane Library (CENTRAL) databases were searched for eligible studies from inception to January 2023. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to evaluate the association between DM and renal functional outcomes using a random effects model. Stata 17.0 software was used for statistical analysis. RESULTS: The meta-analysis included thirteen studies consisting of 8562 RCC patients who underwent nephrectomy. Preoperative comorbidity of DM was significantly associated with poor renal functional outcomes (HR = 1.91, 95% CI 1.48-2.48, p < 0.0001), regardless of ethnicity, follow-up time, body mass index (BMI) and age. However, in the radical nephrectomy subgroup, DM was not significantly associated with renal function decline (HR = 1.91, 95% CI 0.93-3.90, p = 0.0781). CONCLUSIONS: The aggregate evidence indicated that preexisting DM may be associated with poor renal functional outcomes in patients with RCC after nephrectomy, especially in patients receiving partial nephrectomy. Urologists should focus more on the glycemic management of these patients after nephrectomy. More high-quality studies are needed to explore the influence of DM on renal function outcomes in postoperative patients.


Subject(s)
Carcinoma, Renal Cell , Diabetes Mellitus , Kidney Neoplasms , Nephrectomy , Humans , Carcinoma, Renal Cell/surgery , Nephrectomy/methods , Kidney Neoplasms/surgery , Diabetes Mellitus/epidemiology , Treatment Outcome , Kidney/physiopathology
19.
Angew Chem Int Ed Engl ; 63(13): e202317660, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38298160

ABSTRACT

Coordinated manganese (Mn) electrocatalysts owing to their electronic structure flexibility, non-toxic and earth abundant features are promising for electrocatalytic reactions. However, achieving selective hydrogen peroxide (H2 O2 ) production through two electron oxygen reduction (2e-ORR) is a challenge on Mn-centered catalysts. Targeting this goal, we report on the creation of a secondary Mn(II)-coordinated active environment with reactant enrichment effect on boundary-rich porous carbon-based electrocatalysts, which facilitates the selective and rapid synthesis of H2 O2 through 2e-ORR. The catalysts exhibit nearly 100 % Faradaic efficiency and H2 O2 productivity up to 15.1 mol gcat -1 h-1 at 0.1 V versus reversible hydrogen electrode, representing the record high activity for Mn-based electrocatalyst in H2 O2 electrosynthesis. Mechanistic studies reveal that the epoxide and hydroxyl groups surrounding Mn(II) centers improve spin state by modifying electronic properties and charge transfer, thus tailoring the adsorption strength of *OOH intermediate. Multiscale simulations reveal that the high-curvature boundaries facilitate oxygen (O2 ) adsorption and result in local O2 enrichment due to the enhanced interaction between carbon surface and O2 . These merits together ensure the efficient formation of H2 O2 with high local concentration, which can directly boost the tandem reaction of hydrolysis of benzonitrile to benzamide with nearly 100 % conversion rate and exclusive benzamide selectivity.

20.
J Am Chem Soc ; 146(7): 4803-4813, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38335455

ABSTRACT

The design of temperature-adaptive Zn-air batteries (ZABs) with long life spans and high energy efficiencies is challenging owing to sluggish oxygen reduction reaction (ORR) kinetics and an unstable Zn/electrolyte interface. Herein, a quasi-solid-state ZAB is designed by combining atomically dispersed Fe-N-C catalysts containing pyridinic N vacancies (FeNC-VN) with a polarized organo-hydrogel electrolyte. First-principles calculation predicts that adjacent VN sites effectively enhance the covalency of Fe-Nx moieties and moderately weaken *OH binding energies, significantly boosting the ORR kinetics and stability. In situ Raman spectra reveal the dynamic evolution of *O2- and *OOH on the FeNC-VN cathode in the aqueous ZAB, proving that the 4e- associative mechanism is dominant. Moreover, the ethylene glycol-modulated organo-hydrogel electrolyte forms a zincophilic protective layer on the Zn anode surface and tailors the [Zn(H2O)6]2+ solvation sheath, effectively guiding epitaxial deposition of Zn2+ on the Zn (002) plane and suppressing side reactions. The assembled quasi-solid-state ZAB demonstrates a long life span of over 1076 h at 2 mA cm-2 at -20 °C, outperforming most reported ZABs.

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