Personalized embryo transfer guided by rsERT with hourly precision improves pregnancy outcomes in patients with a receptive window of implantation: a pilot study.

PURPOSE: To investigate whether personalized embryo transfer (pET) predicted by a modified RNA-sequencing-based endometrial receptivity test (rsERT) model can improve intrauterine pregnancy rate (IPR) in patients with a receptive window of implantation (WOI). DESIGN: A retrospective pilot study was conducted in the Center for Reproductive Medicine, Central South University, from January 2018 to December 2023. A total of 524 patients with receptive WOI results from rsERT were assigned into two groups based on whether they underwent conventional embryo transfer (conventional ET) or pET. Patients in the conventional ET were matched with those in the pET group at a 1:1 ratio using propensity score matching (PSM). RESULTS: Before PSM, the IPR (55.73% vs. 46.19%, P = 0.032) and implantation rate (IR) (47.51% vs. 34.03%, P = 0.000) in the pET group were significantly higher than that in the conventional ET group. However, the number and types of transferred embryos differed significantly between the two groups. After adjusting for confounding factors, IPR (57.38% vs. 44.81, P = 0.016) and IR (46.81% vs. 33.10%, P = 0.001) remained significantly higher in the pET group compared to the conventional ET group. The implantation failure rate was significantly lower in the pET group compared to controls (42.62% vs. 55.19%, P = 0.016). Additionally, the multiple-pregnancy rate was significantly higher in the pET group compared to the conventional ET group (10.29% vs. 1.68%, P = 0.001). CONCLUSIONS: Women with receptive WOI results could benefit from the receptivity-timed pET predicted by the newly refined rsERT. These findings provide a basis for future research in precision medicine for embryo transfer.

Water periods impact the structure and metabolic potential of the nitrogen-cycling microbial communities in rivers of arid and semi-arid regions.

This study examined the influence of water periods on river nitrogen cycling by analysing nitrogen functional genes and bacterial communities in the Qingshui River, an upstream tributary of the Yellow River in China. Nitrate nitrogen predominated as inorganic nitrogen during the low-flow seasons, whereas salinity was highest during the high-flow seasons. Overall, the functional gene abundance increased with decreasing water volume, and nitrogen concentrations were determined by various specific gene groups. The relative abundance of bacteria carrying these genes varied significantly across water periods. The abundance of Pseudomona, Hydrogenophaga (carrying narGHI and nirB genes), and Flavobacterium (carrying nirK, norBC, and nosZ genes) significantly increased during the low-flow seasons. Nitrogen transformation bacteria exhibited both symbiotic and mutualistic relationships. Microbial network nodes and sizes decreased with decreasing water volume, whereas modularity increased. Additionally, the water period affected the functional microbial community structure by influencing specific environmental factors. Among them, SO42- primarily determined the denitrification, dissimilatory nitrate reduction to ammonium, and assimilatory nitrate reduction to ammonium communities, whereas NO2--N and Mg2+ were the main driving factors for the nitrogen-fixing and nitrifying communities, respectively. These findings have substantial implications for better understanding the reduction in river nitrogen loads in arid and semi-arid regions during different water periods.

Why is vestibular migraine associated with many comorbidities?

Vestibular migraine (VM) is a usual trigger of episodic vertigo. Patients with VM often experience spinning, shaking, or unsteady sensations, which are usually also accompanied by photophobia, phonophobia, motor intolerance, and more. VM is often associated with a number of comorbidities. Recurrent episodes of VM can affect the patient's emotions, sleep, and cognitive functioning to varying degrees. Patients with VM may be accompanied by adverse moods such as anxiety, fear, and depression, which can gradually develop into anxiety disorders or depressive disorders. Sleep disorders are also a common concomitant symptom of VM, which significantly lower patients' quality of life. The influence of anxiety disorders and sleep disorders may reduce cognitive functions of VM, such as visuospatial ability, attention, and memory decline. Clinically, it is also common to see VM comorbid with other vestibular disorders, making the diagnosis more difficult. VM episodes are relieved but lingering, in which case VM may coexist with persistent postural-perceptual dizziness (PPPD). Anxiety may be an important bridge between recurrent VM and PPPD. The clinical manifestations of VM and Meniere's disease (MD) overlap considerably, and those who meet the diagnostic criteria for both can be said to have VM/MD comorbidity. VM can also present with positional vertigo, and some patients with VM present with typical benign paroxysmal positional vertigo (BPPV) nystagmus on positional testing. In this paper, we synthesize and analyze the pathomechanisms of VM comorbidity by reviewing the literature. The results show that it may be related to the extensive connectivity of the vestibular system with different brain regions and the close connection of the trigeminovascular system with the periphery of the vestibule. Therefore, it is necessary to pay attention to the diagnosis of comorbidities in VM, synthesize its pathogenesis, and give comprehensive treatment to patients.

Combined Chemo- and Photothermal Therapies of Non-Small Cell Lung Cancer Using Polydopamine/Au Hollow Nanospheres Loaded with Doxorubicin.

Purpose: The chemotherapeutic agent doxorubicin (DOX) is limited by its cardiotoxicity, posing challenges in its application for non-small cell lung cancer (NSCLC). This study aims to explore the efficacy of polydopamine/Au nanoparticles loaded with DOX for chemotherapy and photothermal therapy in NSCLC to achieve enhanced efficacy and reduced toxicity. Methods: Hollow polydopamine (HPDA)/Au@DOX was synthesized via polydopamine chemical binding sacrificial template method. Morphology was characterized using transmission electron microscopy, particle size and potential were determined using dynamic light scattering, and photothermal conversion efficiency was assessed using near-infrared (NIR) thermal imaging. Drug loading rate and in vitro drug release were investigated. In vitro, anti-tumor experiments were conducted using CCK-8 assay, flow cytometry, and live/dead cell staining to evaluate the cytotoxicity of HPDA/Au@DOX on A549 cells. Uptake of HPDA/Au@DOX by A549 cells was detected using the intrinsic fluorescence of DOX. The in vivo anti-metastasis and anti-tumor effects of HPDA/Au@DOX were explored in mouse lung metastasis and subcutaneous tumor models, respectively. Results: HPDA/Au@DOX with a particle size of (164.26±3.25) nm, a drug loading rate of 36.31%, and an encapsulation efficiency of 90.78% was successfully prepared. Under 808 nm laser irradiation, HPDA/Au@DOX accelerated DOX release and enhanced uptake by A549 cells. In vitro photothermal performance assessment showed excellent photothermal conversion capability and stability of HPDA/Au@DOX under NIR laser irradiation. Both in vitro and in vivo experiments demonstrated that the photothermal-chemotherapy combination group (HPDA/Au@DOX+NIR) exhibited stronger anti-metastatic and anti-tumor activities compared to the monotherapy group (DOX). Conclusion: HPDA/Au@DOX nanosystem demonstrated excellent photothermal effect, inhibiting the growth and metastasis of A549 cells. This nanosystem achieves the combined effect of chemotherapy and photothermal, making it promising for NSCLC treatment.

Inhibition of PRMT5 moderately suppresses prostate cancer growth in vivo but enhances its response to immunotherapy.

Protein arginine methylation is a common post-translational modification (PTM) catalyzed by nine protein arginine methyltransferases (PRMTs). As the major symmetric arginine methyltransferase that methylates both histone and non-histone substrates, PRMT5 plays key roles in a number of biological processes critical for development and tumorigenesis. PRMT5 overexpression has been reported in multiple cancer types including prostate cancer (PCa), but the exact biological and mechanistic understanding of PRMT5 in aggressive PCa remains ill-defined. Here, we show that PRMT5 is upregulated in PCa, correlates with worse patient survival, promotes corrupted RNA splicing, and functionally cooperates with an array of pro-tumorigenic pathways to enhance oncogenesis. PRMT5 inhibition via either genetic knockdown or pharmacological inhibition reduces stemness with paralleled differentiation and arrests cell cycle progression without causing appreciable apoptosis. Strikingly, the severity of antitumor effect of PRMT5 inhibition correlates with disease aggressiveness, with AR+ PCa being less affected. Molecular characterization pinpoints MYC, but not (or at least to a lesser degree) AR, as the main partner of PRMT5 to form a positive feedback loop to exacerbate malignancy in both AR+ and AR- PCa cells. Inspired by the surprising finding that PRMT5 negatively correlates with tumor immune infiltration and transcriptionally suppresses an immune-gene program, we further show that although PRMT5 inhibitor (PRMT5i) EPZ015666 or anti-PD-1 immunotherapy alone exhibits limited antitumor effects, combination of PRMT5i with anti-PD-1 displays superior efficacy in inhibiting castration-resistant PCa (CRPC) in vivo. Finally, to expand the potential use of PRMT5i through a synthetic lethality concept, we also perform a global CRISPR/Cas9 knockout screen to unravel that many clinical-grade drugs of known oncogenic pathways can be repurposed to target CRPC when used in combination with PRMT5i at low doses. Collectively, our findings establish a rationale to exploit PRMT5i in combination with immunotherapy or other targeted therapies to treat aggressive PCa.

[Study on the procoagulant characteristics of microparticles in acute myocardial infarction].

OBJECTIVE: To investigate the characteristic of circulating microparticle in patients with acute myocardial infarction (AMI) and its possible mechanism of promoting coagulation. METHODS: A prospective case-control study was conducted. The patients with coronary heart disease admitted to the second department of cardiology in Harbin First Hospital from June to November 2023 were enrolled, and they were grouped according to whether the patients occurred AMI or not. On the day of admission, disseminated intravascular coagulation (DIC) score was calculated. At the same time, fasting venous blood was collected, and the levels of D-dimer, fibrin degradation product (FDP) and the activities of major coagulation factors were detected. The level of circulating microparticle was determined by microparticle trapping method. The microparticle carrying tissue factor (TF+MP) level was detected by tissue factor (TF) dependent F Xa production assay. Spearman correlation method was used to analyze the correlation among the indicators. RESULTS: A total of 52 patients with coronary heart disease were enrolled, including 26 patients in AMI group and 26 patients in non-AMI group. There was no significant difference in gender, age, body mass index (BMI), underlying diseases, smoking history, and pre-admission treatment of patients between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the non-AMI group, the DIC score and D-dimer, FDP levels in the AMI group were significantly increased [DIC score: 3 (3, 4) vs. 3 (2, 3), D-dimer (mg/L): 8.80 (6.84, 15.66) vs. 2.13 (1.64, 3.86), FDP (mg/L): 30.13 (19.30, 52.54) vs. 20.00 (13.51, 28.37), all P < 0.01], indicating that the degree of coagulation activation in AMI patients was more severe. The consumption of major coagulation factors in the coagulation pathway in the AMI group was heavier than that in the non-AMI group [F II: 59.45% (49.65%, 71.25%) vs. 63.65% (49.98%, 73.22%), F V: 96.95% (73.50%, 112.78%) vs. 105.05% (73.48%, 131.48%), F VII: 42.30% (36.98%, 51.98%) vs. 53.40% (46.58%, 69.88%), F X: 60.90% (48.22%, 80.82%) vs. 73.50% (56.80%, 85.98%), F XI: 82.45% (62.90%, 99.10%) vs. 92.40% (73.90%, 114.25%), F XII: 29.90% (12.42%, 42.38%) vs. 34.65% (16.32%, 48.20%), all P < 0.05]. The circulating TF+MP level in the AMI group was significantly higher than that in the non-AMI group [nmol/L: 0.13 (0.06, 0.20) vs. 0.08 (0.04, 0.15), P < 0.05]. There was no significant difference in the level of circulating microparticle between AMI group and non-AMI group [nmol/L: 1.24 (0.71, 3.77) vs. 1.35 (0.73, 2.14), P > 0.05]. Correlation analysis showed that circulating TF+MP level in the patients with coronary heart disease was significantly positively correlated with coagulation indicator DIC score (r = 0.307, P = 0.027), D-dimer (r = 0.696, P < 0.001) and FDP (r = 0.582, P < 0.001), and there was a strong negative correlation with exogenous pathway factor F VII (r = -0.521, P < 0.001) and common pathway factor F X (r = -0.332, P = 0.016). CONCLUSIONS: The circulating TF+MP level in AMI patients was significantly higher than that in the non-AMI patients. TF+MP may play an important role in activating the extrinsic coagulation pathway, exacerbating coagulation factor consumption, and promoting clot formation during AMI occurrence.

EIF1AX mutation in thyroid nodules: a histopathologic analysis of 56 cases in the context of institutional practices.

EIF1AX mutation has been identified as a driver mutation for papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) study. Subsequent studies confirmed this mutation in PTC and Anaplastic Thyroid Carcinoma (ATC) but also reported EIF1AX mutation in Follicular nodular disease (FND) and benign thyroid nodules. In this study, we review thyroid nodules with EIF1AX mutation from two institutions: a tertiary care hospital (YNHH, n = 22) and a major cancer referral center (MSKCC, n = 34) and report the varying histomorphology in the context of additional genetic abnormalities and institutional practices. Pathology diagnoses were reviewed according to the WHO 5th edition and correlated with the type of EIF1AX mutation and additional concurrent molecular alterations, if any. Most cases were splice site type mutations. Cases consisted of 9 FND, 7 follicular (FA) or oncocytic adenomas (OA), 2 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 38 follicular-cell derived thyroid carcinomas. Of 8 cases with isolated EIF1AX mutation, 7 were FND, FA or OA (88%) and one was an oncocytic carcinoma (12%). Of 12 cases with EIF1AX and one additional molecular alteration, 9 (75%) were FND, FA or OA, 2 (17%) were NIFTPs and one (8%) was a poorly differentiated thyroid carcinoma. All 36 cases with EIF1AX mutation and ≥ 2 molecular alterations were malignant (100%) and included TP53 and TERT promoter mutations associated with ATC (n = 8) and high-grade follicular cell-derived non-anaplastic carcinoma (HGC, n = 2). Isolated EIF1AX mutation was noted only in thyroid nodules seen at YNHH and were predominantly encountered in benign thyroid nodules including FND. Accumulation of additional genetic abnormalities appears to be progressively associated with malignant tumors.

Venous thrombolysis prior to mechanical thrombectomy reduces glycocalyx damage in patients with acute ischemic stroke.

Introduction: The administration of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in the treatment of acute ischemic stroke (AIS) has been a subject of debate, and its potential benefits remain uncertain. This retrospective study aimed to investigate the effect of preoperative IVT on glycocalyx damage in patients with cerebral ischemia-reperfusion injury (IRI). Methods: A cohort of 106 patients with acute large vessel occlusion in the anterior circulation treated with mechanical thrombectomy was enrolled. The levels of the glycocalyx damage marker, syndecan-1, were measured in the peripheral blood of these patients to assess glycocalyx damage during IRI, and clinical outcomes were compared between patients receiving MT alone vs. combined IVT and MT. Results: The study results indicate that thrombolytic drugs have a significant impact on syndecan-1 levels in the blood. Compared to patients who underwent direct MT, those who received preoperative IVT had significantly lower levels of syndecan-1 in their blood. Although preoperative IVT did not alter the final clinical outcomes, the levels of syndecan-1 shedding reflect the extent of damage to the endothelial glycocalyx. Discussion: This suggests that using thrombolytic drugs before mechanical thrombectomy may reduce endothelial glycocalyx damage in patients with ischemia-reperfusion injury. These findings provide indirect clinical evidence supporting the preoperative use of intravenous thrombolysis in such patients.

Enhanced lipid metabolism reprogramming in CHF rats through IL-6-mediated cardiac glial cell modulation by digilanid C and electroacupuncture stimulation combination.

Background: Cardiac lipid metabolism reprogramming is recognized as a critical pathological factor in the progression of chronic heart failure (CHF). The therapeutic potential of digilanid C and electroacupuncture stimulation (ES) in enhancing lipid metabolism and cardiac function has been established. However, the optimal synergistic regulatory strategies of these interventions on cardiac lipid metabolism have yet to be elucidated. Methods: This study aimed to comprehensively evaluate the impact of a digilanid C-ES combination on cardiac steatosis remodeling in CHF. Assessments were conducted across various dimensions, including myocardial oxygen consumption, mitochondrial function, and lipid metabolism. Additionally, we sought to uncover the underlying neuromolecular mechanisms. Results: Our findings, at both molecular and morphological levels, indicated that the synergistic application of digilanid C and ES significantly inhibited myocardial fibrosis and steatosis. This combination therapy facilitated the repair of cardiac neuro-vascular uncoupling and induced a reprogramming of lipid metabolism. Notably, the digilanid C-ES combination ameliorated cardiomyocyte apoptosis and enhanced mitochondrial biogenesis in CHF, leading to a restructured energy supply pattern. Cardiac immunofluorescence analyses revealed the aggregation of cardiac glial cells (CGCs) at sites of abnormal neurovascular coupling, a response to cardiac lipid degeneration. This was accompanied by a marked reduction in the abnormally elevated expression of interleukin 6 (IL-6) and glutamatergic signaling, which correlated with the severity of cardiac steatosis and the aberrant activation of CGCs. The combined therapy was found to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) pathway, effectively attenuated lipid accumulation and over-recruitment of CGCs and deprivation of glutamatergic nerves. Conclusion: These findings underscore the potential of digilanid C and ES combination therapy as a novel approach to modulate the complex interplay between neurovascular dynamics and metabolic dysregulation in CHF.

Bulk and single-cell RNA-seq analyses reveals canonical RNA editing associated with microglial homeostasis and its role in sepsis-associated encephalopathy.

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In the current study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissues and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluated its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and microglial repopulation was primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Moreover, expression of complement-related genes, such as C4b and Cd47, were substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis, and provides new insight into its potential role in SAE.

Histologic spectrum and outcome of Human papillomavirus (HPV)-associated oral cavity squamous cell carcinoma: a single center experience and a survey of The Cancer Genome Atlas (TGCA) cohort.

While high-risk human papillomavirus (HPV) serves as an essential pathogen and an important prognostic and predictive biomarker for oropharyngeal squamous cell carcinoma, it occurs at low frequency (2.2-6%) in oral cavity squamous cell carcinoma (OCSCC). To date, the pathologic features of HPV-associated OCSCC (HPV( +)-OCSCC) have been sparsely reported and its prognosis is not well-defined. We herein described detailed clinicopathologic features and outcomes of a retrospective series of 27 HPV( +)-OCSCC, including 13 from Memorial Sloan Kettering Cancer Center (MSKCC) and 14 from The Cancer Genomic Atlas program (TCGA). The frequency of HPV positivity in OCSCC was 0.7% in MSKCC cohort and 4.9% in TCGA cohort. Although HPV( +)-OCSCC was predominantly non-keratinizing (in 81%) with various degree of maturation, its histologic spectrum was expanded to include keratinizing subtype (19%), adenosquamous carcinoma (7%), and papillary architecture (subtype, 7%). HPV( +)-OCSCC predominantly affected male patients (male:female ratio = 12.5:1) and (ex) smokers (77%). It might occur in mandibular mucosa, floor of mouth, tongue, retromolar trigone, buccal mucosa, maxillary mucosa, or hard palate. In oral cavity, positivity of HPV by RNA in situ hybridization was required, and p16 immunohistochemistry alone was insufficient to confirm the HPV + status. The positive predictive value of p16 immunopositivity in detecting HPV infection was 68%. HPV-positivity did not appear to affect outcomes, including disease specific survival and progression free survival in OCSCC.

Research advances on CaMKs-mediated neurodevelopmental injury.

Calcium/calmodulin-dependent protein kinases (CaMKs) are important proteins in the calcium signaling cascade response pathway, which can broadly regulate biological functions in vivo. Multifunctional CaMKs play key roles in neural development, including neuronal circuit building, synaptic plasticity establishment, and neurotrophic factor secretion. Currently, four familial proteins, calcium/calmodulin-dependent protein kinase I (CaMKI), calcium/calmodulin-dependent protein kinase II (CaMKII), eukaryotic elongation factor 2 kinase (eEF2K, popularly known as CaMKIII) and calcium/calmodulin-dependent protein kinase IV (CaMKIV), are thought to have been the most extensively studied during neurodevelopment. Although their spatial structures are extremely similar, as well as the initial starting point of activation, both require the activation of calcium and calmodulin (CaM) complexes to be involved in the process, and the phosphorylation sites and modes of each member are different. Furthermore, due to the high structural similarity of CaMKs, their members may play synergistic roles in the regulation of neural development, but different CaMKs also have their own means of regulating neural development. In this review, we first describe the visualized protein structural forms of CaMKI, CaMKII, eEF2K and CaMKIV, and then describe the functions of each kinase in neurodevelopment. After that, we focus on four main mechanisms of neurodevelopmental damage caused by CaMKs: CaMKI/ERK/CREB pathway inhibition leading to dendritic spine structural damage; Ca2+/CaM/CaMKII through induction of mitochondrial kinetic disorders leading to neurodevelopmental damage; CaMKIII/eEF2 hyperphosphorylation affects the establishment of synaptic plasticity; and CaMKIV/JNK/NF-κB through induction of an inflammatory response leading to neurodevelopmental damage. In conclusion, we briefly discuss the pathophysiological significance of aberrant CaMK family expression in neurodevelopmental disorders, as well as the protective effects of conventional CaMKII and CaMKIII antagonists against neurodevelopmental injury.

Tiaogan Bushen Xiaoji Formula Enhances the Sensitivity of Estrogen Receptor- Positive Breast Cancer to Tamoxifen by Inhibiting the TGF-ß/SMAD Pathway.

Background: The resistance to endocrine therapy can lead to recurrence and metastasis of breast cancer (BC), affecting the survival period. Tiaogan Bushen Xiaoji (TGBSXJ) Formula, a traditional Chinese medicine (TCM) decoction, has been widely used in the treatment of estrogen receptor-positive (ER+) BC. However, the underlying mechanism of TGBSXJ Formula in ER+BC treatment has not been totally elucidated. Methods: Network pharmacology (NP) and RNA sequencing were used to predict the candidate ingredients and explore the potential targets of TGBSXJ Formula. Then, the results of NP and RNA sequencing were investigated by in vitro experiments. Results: Active ingredients of TGBSXJ Formula mainly included Mangiferin, Rutin, Anemarrhena asphodeloides saponin BII, Ganoderic acid A and Acacetin, etc. A protein-protein interaction (PPI) network was created based on the active ingredients of TGBSXJ Formula and target genes of ER+ BC, in which TGF-ß, MMP2 and SMAD3 were defined as the hub genes. In vitro experiments showed that TGBSXJ Formula significantly inhibited the viability, colony ability and migration of ER+ BC cells, and significantly increased the sensitivity to TAM. Western blot analysis showed that TGBSXJ Formula significantly downregulated TGF-ß, E-cadherin, MMP2, MMP9, N-cadherin, p-Smad2 and p-Smad3 in ER+ BC cells. Conclusion: TGBSXJ Formula increases the sensitivity of ER+ BC cells to TAM by inhibiting the TGF-ß/Smad signaling pathway.

Boosting circularly polarized luminescence by optimizing off-centering octahedral distortion in zero-dimensional hybrid indium-antimony halides.

Chiral zero-dimensional hybrid metal halides (0D HMHs) are being extensively studied as they can directly generate circularly polarized luminescence (CPL) with high photoluminescence quantum yields (PLQYs), yet improving their luminescence dissymmetry factor (g lum) remains a challenge. This study proposes a general strategy to boost the g lum value of chiral 0D HMHs by optimizing the off-centering distortion of inorganic octahedra. Accordingly, (R/S-MBA)2(2MA)In0.95Sb0.05Cl6 (MBA = α-methylbenzylammonium, 2MA = dimethylamine) and (R/S-MBA)2(3MA)In0.95Sb0.05Cl6 (3MA = trimethylamine) with near-unity PLQYs are accordingly synthesized. With increasing the from 0.012 to 0.020, the |g lum| is accordingly increased from 7.8 × 10-3 to 2.0 × 10-2. Notably, the |g lum| can be further boosted to an impressive value of 3.8 × 10-2 while maintaining near-unity PLQYs by continuously increasing the . Experimental results reveal that the choice of achiral ligands and varied Sb3+ dopant concentrations can modulate the distribution and strength of hydrogen bonds around indium-antimony halogen octahedra, respectively, thus regulating the parameter of octahedra in 0D hybrid metal halides. Additionally, light-emitting diodes with a polarization of 1.6% are fabricated. This work sheds light on the relationship between the distortion of inorganic octahedra and the g lum value.

Preoperative systemic and local inflammation are independent risk factors for difficult laparoscopic cholecystectomy after percutaneous transhepatic gallbladder drainage.

Background: Laparoscopic cholecystectomy (LC) is required for acute cholecystitis patient with percutaneous transhepatic gallbladder drainage (PTGBD). However, it's unknown how to distinguishing the surgical difficulty for these patients. Methods: Data of patients who underwent LC after PTGBD between 2016 and 2022 were collected. Patients were categorized into difficult and non-difficult operations based on operative time, blood loss, and surgical conversion. Performance of prediction model was evaluated by ROC, calibration, and decision curves. Results: A total of 127 patients were analyzed, including 91 in non-difficult operation group and 36 in difficult operation group. Elevated CRP (P = 0.011), pericholecystic effusion (P < 0.001), and contact with stomach or duodenal (P = 0.015) were independent risk factors for difficult LC after PTGBD. A nomogram was developed according to these risk factors, and was well-calibrated and good at distinguishing difficult LC after PTGBD. Conclusion: Preoperative elevated systemic and local inflammation indictors are predictors for difficult LC after PTGBD.

Conformation-Confined Organic Butterfly-Molecule with High Photoluminescence Efficiency, Deep-Blue Amplified Spontaneous Emission, and Unique Piezochromic Luminescence.

Organic fluorophores with tunable π-conjugated paths have attracted considerable attention owing to their diverse properties and promising applications. Herein, we present a tailored butterfly like molecule, 2,2'-(2,5-bis (2,2-diphenylvinyl)-1,4-phenylene)dinaphtha-lene (BDVPN), which exhibits diverse photophysical features in its two polymorphs. The BP phase crystal, with its "aligned wings" conformation, possesses emissive characteristics that are nearly identical to those in dilute solutions. In contrast, the BN phase crystal, which adopts an "orthogonal wings" conformation, exhibits an unusual hypsochromic-shifted emission compared to its dilute solution counterparts. This intriguing hypsochromic-shifted emission originates from the reduction in the effective conjugated length of the molecular skeleton. Notably, BN phase crystals also exhibit exceptional optical performance, featuring high-efficiency emission (76.6%), low-loss optical waveguides (0.571 dB mm-1), deep-blue amplified spontaneous emission (ASE) with a narrow full width at half maximum (FWHM: 6.4 nm), and a unique 200 nm bathochromic shift of piezochromic luminescence.

Comparative Study Between Variable Flip Angle and Modified Look-Locker Inversion Recovery for Evaluating Renal Interstitial Fibrosis.

BACKGROUND: Variable flip angle (VFA) and modified Look-Locker inversion recovery (MOLLI) are frequently used for noninvasive evaluation of renal interstitial fibrosis (IF) in chronic kidney disease (CKD). However, controversy remains over which method is preferred. PURPOSE: To compare the diagnostic efficacy of VFA and MOLLI for T1 mapping in evaluating renal IF. STUDY TYPE: Prospective. SUBJECTS: Fifty-one participants with CKD (CKD stage 1-5, 35 males) and 18 healthy volunteers (eight males). FIELD STRENGTH/SEQUENCE: 3.0 T, three-dimensional gradient echo sequence for B1+ VFA, and two-dimensional gradient echo sequence for MOLLI. ASSESSMENT: Image quality was assessed on a five-point scale. Cortex and medulla T1 values (cT1 and mT1), corticomedullary T1 value difference (ΔT1, medulla - cortex), and corticomedullary T1 value ratio (ratio T1, cortex:medulla) were compared between VFA and MOLLI as well as between IF grade (0-4) based on biopsy. STATISTICAL TESTS: Intraclass correlation coefficient, Bland-Altman analysis, analysis of variance, Kruskal-Wallis test, correlation analysis, and receiver operating characteristics analysis with the area under the curve (AUC). P-value <0.05 was considered significant. RESULTS: MOLLI provided significantly better image quality compared to VFA. cT1 and mT1 values significantly differed between VFA and MOLLI (cT1-VFA: 1771.4 ± 139.4 msec vs. cT1-MOLLI: 1729.9 ± 132.1 msec; mT1-VFA: 2076.0 [interquartile range (IQR): 2045.9-2129.9] msec vs. mT1-MOLLI: 2039.2 [IQR: 1997.8-2071.6] msec). ΔT1 and ratio T1 values were not different between VFA and MOLLI (ΔT1: 300.8 ± 71.4 vs. 306.0 ± 78.4, respectively, P = 0.33 and ratio T1: 0.85 ± 0.038 vs. 0.85 ± 0.041, respectively, P = 0.064). No difference was observed between T1 variables and T1 mapping methods in diagnosing IF. DATA CONCLUSION: ΔT1 and ratio T1 were not different between VFA and MOLLI. Both VFA and MOLLI are effective for noninvasive assessment of renal IF. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Heterogeneous porous hypoxia-mimicking scaffolds propel urethral reconstruction by promoting angiogenesis and regulating inflammation.

The nasty urine microenvironment (UME) impedes neourethral regeneration by inhibiting angiogenesis and inducing an excessive inflammatory response. Cellular adaptation to hypoxia improves regeneration in numerous tissues. In this study, heterogeneous porous hypoxia-mimicking scaffolds were fabricated for urethral reconstruction via promoting angiogenesis and modulating the inflammatory response based on sustained release of dimethyloxalylglycine (DMOG) to promote HIF-1α stabilization. Such scaffolds exhibit a two-layered structure: a dense layer composed of electrospun poly (l-lactic acid) (PLLA) nanofibrous mats and a loose layer composed of a porous gelatin matrix incorporated with DMOG-loaded mesoporous silica nanoparticles (DMSNs) and coated with poly(glycerol sebacate) (PGS). The modification of PGS could significantly increase rupture elongation, making the composite scaffolds more suitable for urethral tissue regeneration. Additionally, sustained release of DMOG from the scaffold facilitates proliferation, migration, tube formation, and angiogenetic gene expression in human umbilical vein endothelial cells (HUVECs), as well as stimulates M2 macrophage polarization and its regulation of HUVECs migration and smooth muscle cell (SMCs) contractile phenotype. These effects were downstream of the stabilization of HIF-1α in HUVECs and macrophages under hypoxia-mimicking conditions. Furthermore, the scaffold achieved better urethral reconstruction in a rabbit urethral stricture model, including an unobstructed urethra with a larger urethral diameter, increased regeneration of urothelial cells, SMCs, and neovascularization. Our results indicate that heterogeneous porous hypoxia-mimicking scaffolds could promote urethral reconstruction via facilitating angiogenesis and modulating inflammatory response.