Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD). METHODS: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding. RESULTS: Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively. CONCLUSIONS: EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.

Optimizing removal of antiretroviral drugs from tertiary wastewater using chlorination and AI-based prediction with response surface methodology.

Chemical and pharmaceutical chemicals found in water sources create substantial risks to human health and the environment. The presence of pharmaceutical contaminants in water can cause antibiotic resistance development, toxicity to aquatic organisms, and endocrine disruption. Hence, the elimination of chemicals and other contaminants from wastewater prior to its release is a burgeoning concern in the domains of engineering and science. The use of treatment technologies in wastewater treatment plants can remove pharmaceutical contaminants through the oxidation process. However, many traditional wastewater treatment plants lack the advanced monitoring tools required to detect low concentrations of pharmaceuticals. Without the ability to detect these compounds, it's challenging to treat them effectively. The goal of this study was to use Response Surface Methodology (RSM) and Artificial Neural Networks (ANN) algorithms to model and improve how Nevirapine and Efavirenz break down in different chlorination conditions. The RSM analysis revealed statistically significant models (F-values: Nevirapine, pH-t: 108.15, T-t: 76.55, ICC-t: 110.84), indicating a strong correlation between operational parameters (pH, temperature, and initial chlorine concentration) and degradation behavior. The ANN model accurately predicted the degradation of both Nevirapine and Efavirenz under various chlorination conditions, as confirmed by analyzing actual-predicted graphs, residual plots, and Mean Squared Error (MSE) values. The ANN model using ICC-t achieved the highest MOD value of 31.31 % for Nevirapine. The ANN model based on ICC-t yielded a maximum MOD value of 16.06 % for Efavirenz. These findings provide valuable insights into optimizing chlorination processes for better removal of these pharmaceutical contaminants from water.

Roles of glutamic pyruvate transaminase 2 in reprogramming of airway epithelial lipidomic and metabolomic profiles after smoking.

Metabolic abnormalities represent one of the pathological features of chronic obstructive pulmonary disease (COPD). Glutamic pyruvate transaminase 2 (GPT2) is involved in glutamate metabolism and lipid synthesis pathways, whilst the exact roles of GPT2 in the occurrence and development of COPD remains uncertain. This study aims at investigating how GPT2 and the associated genes modulate smoking-induced airway epithelial metabolism and damage by reprogramming lipid synthesis. The circulating or human airway epithelial metabolomic and lipidomic profiles of COPD patients or cell-lines explored with smoking were assessed to elucidate the pivotal roles of GPT2 in reprogramming processes. We found that GPT2 regulate the reprogramming of lipid metabolisms caused by smoking, especially phosphatidylcholine (PC) and triacylglycerol (TAG), along with changes in the expression of lipid metabolism-associated genes. GPT2 modulated cell sensitivities and survival in response to smoking by enhancing mitochondrial functions and maintaining lipid and energy homeostasis. Our findings provide evidence for the involvement of GPT2 in the reprogramming of airway epithelial lipids following smoking, as well as the molecular mechanisms underlying GPT2-mediated regulation, which may offer an alternative of therapeutic strategies for chronic lung diseases.

Knowledge, Attitudes, and Practices Among Elderly CHD Patients Towards Self-Perceived Health Abilities.

Objective: This study aimed to assess the knowledge, attitudes and practices (KAP) among elderly coronary heart disease (CHD) patients toward self-perceived health abilities. Methods: This web-based study was carried out between April 2023 and September 2023 at Guang'anmen Hospital, China Academy of Chinese Medical Sciences. A self-developed questionnaire was utilized to collect demographic information from elderly CHD patients, and evaluate their KAP towards self-perceived health abilities. Results: A total of 568 valid questionnaires were collected. Among the participants, the average age was 65.97±5.50 years, and 298 (52.46%) were female, and the mean scores for knowledge, attitudes, and practices were 6.34±2.29 (possible range: 0-9), 35.24±4.99 (possible range: 9-45), and 27.79±10.09 (possible range: 9-45), respectively. The structural equation model demonstrated that elderly CHD patients' knowledge directly affects attitudes and practices, with path coefficient of 0.93 (P<0.001) and 0.39 (P=0.033), respectively. Moreover, attitudes play an intermediary role between knowledge and practice with path coefficient of 0.75 (P<0.001). Furthermore, residence directly affects knowledge with path coefficient of 0.67 (P<0.001), cardiac function directly affects knowledge with path coefficient of -0.97 (P<0.001) and history of interventional therapy directly affects practice with path coefficient of 4.23 (P<0.001). Conclusion: Elderly CHD patients demonstrated sufficient knowledge, positive attitudes, and proactive practices towards self-perceived health abilities. However, educational programs and behavior modification are recommended, particularly for elderly with lower age and education, living in rural areas, lacking interventional therapy, obese, or taking multiple CHD medications.

A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.

OBJECTIVE: Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. DESIGN, PATIENTS AND MEASUREMENTS: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. RESULTS: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). CONCLUSIONS: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.

Ir(III) Metal Emitters with Cyano-Modified Imidazo[4,5-b]pyridin-2-ylidene Chelates for Deep-Blue Organic Light-Emitting Diodes.

Ir(III) carbene complexes have been explored as one of the best blue phosphors for their high performance. Herein, the authors designed and synthesized a series of blue-emitting Ir(III) phosphors (f-ct9a-c), featuring fac-coordinated cyano-imidazo[4,5-b]pyridin-2-ylidene cyclometalates. These Ir(III) complexes exhibit true-blue emission with a peak maximum spanning 448-467 nm, with high photoluminescence quantum yields of 81-88% recorded in degassed toluene. Moreover, OLED devices bearing phosphors f-ct9a and f-ct9b deliver maximum external quantum efficiencies (EQEmax) of 25.9% and 30.3%, together with Commission Internationale de L'Eclairage (CIEx,y) coordinates of (0.157, 0.225) and (0.142, 0.169), respectively. Remarkably, the f-ct9b-based device displays an incredible EQE of 29.0% at 5000 cd·m-2. The hyper-OLED device based on f-ct9b and ν-DABNA exhibits an EQEmax of 34.7% and CIEx,y coordinates of (0.122, 0.131), affirming high potentials in achieving efficient blue electroluminescence.

Boosting Blue Self-Trapped Exciton Emission in All-Inorganic Zero-Dimensional Metal Halide Cs2ZnCl4 via Zirconium (IV) Doping.

Low-dimensional metal halides with efficient luminescence properties have received widespread attention recently. However, nontoxic and stable low-dimensional metal halides with efficient blue emission are rarely reported. We used a solvothermal synthesis method to synthesize tetravalent zirconium ion-doped all-inorganic zero-dimensional Cs2ZnCl4 for the first time. Bright blue emission in the range of 370 nm-700 nm with a emission maximum at 456 nm was observed in Zr4+:Cs2ZnCl4 accompanied by a large Stokes shift, which was due to self-trapped excitons (STEs) caused by the lattice vibrations of the twisted structure. Simultaneously, the PLQY of Zr4+:Cs2ZnCl4 achieve an impressive 89.67%, positioning it as a compelling contender for future applications in blue-light technology.

Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis.

The long-term high-fat diet (HFD) can cause myocardial lipotoxicity, which is characterized pathologically by myocardial hypertrophy, fibrosis, and remodeling and clinically by cardiac dysfunction and heart failure in patients with obesity and diabetes. Circular RNAs (circRNAs), a novel class of noncoding RNA characterized by a ring formation through covalent bonds, play a critical role in various cardiovascular diseases. However, few studies have been conducted to investigate the role and mechanism of circRNA in myocardial lipotoxicity. Here, we found that circ_005077, formed by exon 2-4 of Crmp1, was significantly upregulated in the myocardium of an HFD-fed rat. Furthermore, we identified circ_005077 as a novel ferroptosis-related regulator that plays a role in palmitic acid (PA) and HFD-induced myocardial lipotoxicity in vitro and in vivo. Mechanically, circ_005077 interacted with Cyclophilin A (CyPA) and inhibited its degradation via the ubiquitination proteasome system (UBS), thus promoting the interaction between CyPA and p47phox to enhance the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase responsible for ROS generation, subsequently inducing ferroptosis. Therefore, our results provide new insights into the mechanisms of myocardial lipotoxicity, potentially leading to the identification of a novel therapeutic target for the treatment of myocardial lipotoxicity in the future.

Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis.

BACKGROUND: The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens. METHODS: The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history. RESULTS: Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38-0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26-0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25-0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31-0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28-0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associated with the best PFS and OS benefits. CONCLUSION: For patients with advanced non-selective PD-L1 NSCLC, two effective regimens are Pen + CT and Niv + Bev + CT, which rank first in OS and PFS among all patients. Cam + CT and Tor + CT have advantages for OS in patients with SqNSCLC and Non-sqNSCLC, respectively. Niv + Ipi + CT provided the best OS benefit for patients with an ECOG score of 0, while Pem + CT may be the most effective treatment for patients with an ECOG score of 1. Pem + CT has a better effect on female patients and non-smokers. Sin + CT was found to be the most effective treatment for male patients and the smoking subgroup, while Cam + CT was found to be the most effective for PFS. In addition, Tor + CT was associated with the best PFS for patients with negative PD-L1 expression. Pem + CT was found to significantly improve both PFS and OS compared to CT alone. For patients with positive PD-L1 expression, Sin + CT and Cam + CT were found to be optimal for OS and PFS, respectively. It is important to note that, with the exception of Tor + CT, the toxicity of the other combinations was higher than that of CT alone.

A chemiluminescence immunoassay for type IV collagen as a promising marker for liver fibrosis and cirrhosis.

Herein, a magnetic bead-based chemiluminescence assay is reported to detect type IV collagen (col-IV) in serum samples. Magnetic beads (MBs) exhibit biocompatibility. Taking advantage of this property, they were conjugated with the col-IV antibody. For the determination of col-IV, the interaction of the col-IV sample, anti-(col-IV)-alkaline phosphatase (anti-(col-IV)-ALP) and anti-col-IV-magnetic beads (anti-(col-IV)-MBs) was performed to generate chemiluminescence. Under the optimized conditions, the developed method displayed good linearity in the concentration range of 20-2000 ng mL-1 with the limit of 0.79 ng mL-1. The repeatability coefficient of variation (CV) for col-IV detection ranged from 3.16% to 7.50%. The col-IV level in samples collected from a hospital was assessed by the chemiluminescence assay. Satisfactory recoveries were obtained ranging from 93.30% to 100.14%. In conclusion, the magnetic bead-based chemiluminescence assay may be used as a routine and efficient tool to detect type IV collagen in clinical diagnosis.

Association between polymorphism in the MTHFR gene and encephaloduroarteriosynangiosis-induced collateral circulation formation.

OBJECTIVE: This study aimed to investigate whether high homocysteine (Hcy) levels associated with the MTHFR gene influence the formation of the collateral vascular network in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis (EDAS) by influencing the number of endothelial progenitor cells (EPCs) in peripheral blood. METHODS: A total of 118 Chinese patients with bilateral primary MMD were prospectively included. Blood samples were collected from the anterior cubital vein before surgery, and MTHFR rs9651118 was genotyped using high-throughput mass spectrometry to determine the genotype of the test specimen. Serum Hcy and EPC levels were measured, the latter with flow cytometry. Digital subtraction angiography was performed 6 months after EDAS, and the formation of collateral circulation was evaluated using the Matsushima grade system. The correlations between MTHFR rs9651118 genotype, Hcy and EPC levels, and Matsushima grade were compared. RESULTS: Among the 118 patients, 53 had the TT genotype (wild type) of MTHFR rs9651118, 33 TC genotype (heterozygous mutation), and 32 CC genotype (homozygous mutation). The mean ± SD Hcy level was 13.4 ± 9.5 µmol/L in TT patients, 9.8 ± 3.2 µmol/L in TC patients, and 8.9 ± 2.9 µmol/L in CC patients (p < 0.001). The level of EPCs in the venous blood of TT patients was 0.039% ± 0.016%, that of TC patients 0.088% ± 0.061%, and that of CC patients 0.103% ± 0.062% (p < 0.001). When the rs9651118 gene locus was mutated, Matsushima grade was better (p < 0.001) but there was no difference between heterozygous and homozygous mutations. CONCLUSIONS: The results suggest that the MTHFR rs9651118 polymorphism is a good biomarker for collateral vascular network formation after EDAS in MMD patients.

Mn(II)-Activated Zero-Dimensional Zinc(II)-Based Metal Halide Hybrids with Near-Unity Photoluminescence Quantum Yield.

As derivatives of metal halide perovskite materials, low-dimensional metal halide materials have become important materials that have attracted much attention in recent years. As one branch, zinc-based metal halides have the potential for practical applications due to their lead-free, low-toxicity and high-stability characteristics. However, pure zinc-based metal halide materials are still limited by their poor optical properties and cannot achieve large-scale practical applications. Therefore, in this work, we report an organic-inorganic hybrid zero-dimensional zinc bromide, (TDMP)ZnBr4, using transition metal Mn2+ ions as dopants and incorporating them into the (TDMP)ZnBr4 lattice. The original non-emissive (TDMP)ZnBr4 exhibits bright green emission under the excitation of external UV light after the introduction of Mn2+ ions with a PL peak position located at 538 nm and a PLQY of up to 91.2%. Through the characterization of relevant photophysical properties and the results of theoretical calculations, we confirm that this green emission in Mn2+:(TDMP)ZnBr4 originates from the 4T1 → 6A1 optical transition process of Mn2+ ions in the lattice structure, and the near-unity PLQY benefits from highly localized electrons generated by the unique zero-dimensional structure of the host material (TDMP)ZnBr4. This work provides theoretical guidance and reference for expanding the family of zinc-based metal halide materials and improving and controlling their optical properties through ion doping.

High Level of Serum Complement C3 Expression is Associated with Postoperative Vasculopathy Progression in Moyamoya Disease.

Background: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD. Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression. Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003*). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001*). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006*), diastolic blood pressure (P=0.004*) and serum complement C3 expression (P=0.015*) were associated with vasculopathy progression after adjusting different covariables. Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late-Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.

Color-Tunable Organic Light-Emitting Diodes with Single Pt (O

Color-tunable organic light-emitting diodes (CT-OLEDs) have a large color-tuning range, high efficiency and operational stability at practical luminance, making them ideal for human-machine interactive terminals of wearable biomedical devices. However, the device operational lifetime of CT-OLEDs is currently far from reaching practical requirements. To address this problem, a tetradentate Pt(II) complex named tetra-Pt-dbf, which can emit efficiently in both monomer and aggregation states, is designed. This emitter has high Td of 508 °C and large intermolecular bonding energy of -52.0 kcal mol⁻1, which improve its thermal/chemical stability. This unique single-emitter CT-OLED essentially avoids the "color-aging issue" and achieves a large color-tuning span (red to yellowish green) and a high external quantum efficiency （EQE） of ≈30% at 1000 cd m-2 as well as an EQE of above 25% at 10000 cd m-2. A superior LT90 operational lifetime of 520,536 h at a functional luminance of 100 cd m-2, which is over 20 times longer than the state-of-the-art CT-OLEDs, is estimated. To demonstrate the potential application of such OLEDs in wearable biomedical devices, a simple electromyography (EMG)-visualization system is fabricated using the CT-OLEDs.

Analysing a Group of Homologous BAHD Enzymes Provides Insights into the Evolutionary Transition of Rosmarinic Acid Synthases from Hydroxycinnamoyl-CoA:Shikimate/Quinate Hydroxycinnamoyl Transferases.

The interplay of various enzymes and compounds gives rise to the intricate secondary metabolic networks observed today. However, the current understanding of their formation and expansion remains limited. BAHD acyltransferases play important roles in the biosynthesis of numerous significant secondary metabolites. In plants, they are widely distributed and exhibit a diverse range of activities. Among them, rosmarinic acid synthase (RAS) and hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase (HCT) have gained significant recognition and have been extensively investigated as prominent members of the BAHD acyltransferase family. Here, we conducted a comprehensive study on a unique group of RAS homologous enzymes in Mentha longifolia that display both catalytic activities and molecular features similar to HCT and Lamiaceae RAS. Subsequent phylogenetic and comparative genome analyses revealed their derivation from expansion events within the HCT gene family, indicating their potential as collateral branches along the evolutionary trajectory, leading to Lamiaceae RAS while still retaining certain ancestral vestiges. This discovery provides more detailed insights into the evolution from HCT to RAS. Our collective findings indicate that gene duplication is the driving force behind the observed evolutionary pattern in plant-specialized enzymes, which probably originated from ancestral enzyme promiscuity and were subsequently shaped by principles of biological adaptation.

Bone mineral density in adults growth hormone deficiency with different ages of onset: a real-world retrospective study.

PURPOSE: Bone mineral density (BMD) impairment is one of the critical factors for long-term quality of life in adults growth hormone deficiency (AGHD). This study aims to investigate the annual changes in BMD in AGHD patients with different ages of onset and to identify predicting factors that influence BMD. METHODS: AGHD patients (n = 160) with available data for 4 years follow-up from a major tertiary medical center in China were retrospectively included (110 [68.8%] childhood-onset, 119 [74.4%] male). BMD of the axial bone (including total hip, neck of femur, and L1-4) derived from dual X-ray absorptiometry and final height were investigated at the first visit, 12 months, 24 months, 36 months, and 48 months thereafter. Low BMD was defined as Z-score ≤ -2. RESULTS: The prevalence of low BMD was 30.0% at baseline and 12.5% at 4 years of follow-up. The CO AGHD group presented a significantly lower BMD than the AO AGHD group at the baseline (P = 0.009). In contrast, the CO AGHD group had significantly greater median annual BMD change than the AO AGHD group (0.044 vs. -0.0003 g/cm2/year in L1-4, P < 0.001), indicating a significant difference in the overall BMD trend between CO and AO groups. Childhood-onset (odds ratio [OR] 0.326, P = 0.012), low serum testosterone (OR 0.847; P = 0.004) and FT4 (OR 0.595; P = 0.039) level were independent risk factors for BMD loss. CONCLUSION: The annual changes of BMD show a different pattern in AGHD patients with varying ages of onset. Patients with CO AGHD have a lower bone mass, and in general, appropriate replacement therapy is necessary for long-term bone health in AGHD patients.

Synthesis and Properties of Injectable Hydrogel for Tissue Filling.

Hydrogels with injectability have emerged as the focal point in tissue filling, owing to their unique properties, such as minimal adverse effects, faster recovery, good results, and negligible disruption to daily activities. These hydrogels could attain their injectability through chemical covalent crosslinking, physical crosslinking, or biological crosslinking. These reactions allow for the formation of reversible bonds or delayed gelatinization, ensuring a minimally invasive approach for tissue filling. Injectable hydrogels facilitate tissue augmentation and tissue regeneration by offering slow degradation, mechanical support, and the modulation of biological functions in host cells. This review summarizes the recent advancements in synthetic strategies for injectable hydrogels and introduces their application in tissue filling. Ultimately, we discuss the prospects and prevailing challenges in developing optimal injectable hydrogels for tissue augmentation, aiming to chart a course for future investigations.

Stereo effects for efficient synthesis of orange-red multiple resonance emitters centered on a pyridine ring.

Despite theoretical difficulties, we herein demonstrate an effective strategy for the inaugural synthesis of an orange-red multiple resonance (MR) emitter centered on a pyridine ring via stereo effects. Compared to conventional benzene-centered materials, the pyridine moiety in the novel MR material acts as a co-acceptor. This results in a significant spectral redshift and a narrower spectrum, as well as an improved photoluminescence quantum yield (PLQY) due to the formation of intramolecular hydrogen bonds. As envisioned, the proof-of-concept emitter Py-Cz-BN exhibits bright orange-red emission peaking at 586 nm with a small full width at half maximum (FWHM) of 0.14 eV (40 nm), exceeding both the wavelength and FWHM achieved with benzene-centered BBCz-Y. Benefiting from high PLQYs (>92%) and suppressed chromophore interactions, the optimized organic light-emitting diodes achieved high maximum external quantum efficiencies of 25.3-29.6%, identical small FWHMs of 0.18 eV (54 nm), and long lifetimes over a wide range of dopant concentrations (1-15 wt%). The performance described above demonstrates the effectiveness of this molecular design and synthesis strategy in constructing high performance long-wavelength MR emitters.