Skeletal Formation of Carbocycles with CO2: Selective Synthesis of Indolo[3,2-b]carbazoles or Cyclophanes from Indoles, CO2, and Phenylsilane.

The catalytic reactions of indoles with CO2 and phenylsilane afforded indolo[3,2-b]carbazoles, where the fused benzene ring was constructed by forming two C-H bonds and four C-C bonds with two CO2 molecules via deoxygenative conversions. Nine-membered cyclophanes made up of three indoles and three CO2 molecules were also obtained, where the cyclophane framework was constructed by forming six C-H bonds and six C-C bonds. These multicomponent cascade reactions giving completely different carbocycles were switched simply by choosing the solvent, acetonitrile or ethyl acetate.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Campylotropis xinfeniae (Fabaceae, Papilionoideae), a new species from Yunnan, China, based on morphological and molecular evidence.

Campylotropis xinfeniae, a new species from the dry-hot valley of the Jinsha River in the Yunnan province, China, is described and illustrated. It is morphologically similar to C. wilsonii and C. brevifolia in having glabrescent old branches, absent stipels, 3-foliolate leaves, and adaxially puberulent leaflets, while it differs from the latter two in having often paniculate inflorescences, obviously white standard, not incurved sickle keel, larger narrowly oblique legumes, and longer legume beak. The complete chloroplast genome of this new species is 149,073 bp in length and exhibits a typical quadripartite structure. Phylogenetic analyses based on the complete chloroplast genome also supported C. xinfeniae as a new species located at the basal distinct clade of the genus Campylotropis, clearly separated from the remaining members of the genus and its allied genera. A conservation assessment of data deficient (DD) is recommended for the new species without extensive exploring of similar habitats according to the IUCN Categories and Criteria.

Homochiral and Heterochiral Self-Sorting Assemblies of Antiaromatic Ni(II) Norcorrole Dimers.

Recently, π-π stacked antiaromatic π-systems have received considerable attention because they can exhibit stacked-ring aromaticity due to substantial intermolecular orbital interactions. Here, we report three antiaromatic norcorrole dimers that self-assemble to form supramolecular architectures through chiral self-sorting. A 2,2'-linked norcorrole dimer with 3,5-di-tert-butylphenyl groups forms a π-stacked dimer both in solid and solution states via homochiral self-sorting. Its association constant in solution is (3.6 ± 1.7) × 105 M-1 at 20 °C. In the solid state, 3,3'-linked norcorrole dimers with 3,5-di-tert-butylphenyl and phenyl groups afford macrocyclic and helical supramolecular assemblies via heterochiral and homochiral self-sorting, respectively. Notably, the subtle modification in the substituent resulted in a complete change in the structure of the aggregates and the chiral self-sorting mode. The present findings demonstrate that structural manipulation in antiaromatic monomer units leads to the formation of various supramolecular assemblies on the basis of the attractive interactions between antiaromatic π-systems.

LTA and PGN from Bacillus siamensis can alleviate soybean meal-induced enteritis and microbiota dysbiosis in Lateolabrax maculatus.

An eight-week feeding trial was designed to assess which component of commensal Bacillus siamensis LF4 can mitigate SBM-induced enteritis and microbiota dysbiosis in spotted seabass (Lateolabrax maculatus) based on TLRs-MAPKs/NF-кB signaling pathways. Fish continuously fed low SBM (containing 16 % SBM) and high SBM (containing 40 % SBM) diets were used as positive (FM group) and negative (SBM group) control, respectively. After feeding high SBM diet for 28 days, fish were supplemented with B. siamensis LF4-derived whole cell wall (CW), cell wall protein (CWP), lipoteichoic acid (LTA) or peptidoglycan (PGN) until 56 days. The results showed that a high inclusion of SBM in the diet caused enteritis, characterized with significantly (P < 0.05) decreased muscular thickness, villus height, villus width, atrophied and loosely arranged microvillus. Moreover, high SBM inclusion induced an up-regulation of pro-inflammatory cytokines and a down-regulation of occludin, E-cadherin, anti-inflammatory cytokines, apoptosis related genes and antimicrobial peptides. However, dietary supplementation with CW, LTA, and PGN of B. siamensis LF4 could effectively alleviate enteritis caused by a high level of dietary SBM. Additionally, CWP and PGN administration increased beneficial Cetobacterium and decreased pathogenic Plesiomonas and Brevinema, while dietary LTA decreased Plesiomonas and Brevinema, suggesting that CWP, LTA and PGN positively modulated intestinal microbiota in spotted seabass. Furthermore, CW, LTA, and PGN application significantly stimulated TLR2, TLR5 and MyD88 expressions, and inhibited the downstream p38 and NF-κB signaling. Taken together, these results suggest that LTA and PGN from B. siamensis LF4 could alleviate soybean meal-induced enteritis and microbiota dysbiosis in L. maculatus, and p38 MAPK/NF-κB pathways might be involved in those processes.

Pulsed electric field treatment improves the oil yield, quality, and antioxidant activity of virgin olive oil.

Pulsed electric field (PEF) is an innovative technique used to assist in the extraction of vegetable oils. There has been no research on the effects of PEF on virgin olive oil (VOO) quality and antioxidant activity to date. The present study aimed to analyze the effects of PEF on oil yield, quality, and in vitro antioxidant activity of "Koroneiki" extra virgin olive oil. The results show that the PEF treatment increased the oil yield by 5.6%, but had no significant effect on the saponification value, K232, K270, and ∆K value of the VOO. PEF treatment reduced the oleic acid content by 3.12%, but had no significant effect on the content of palmitic acid, linoleic acid, linolenic acid, arachidonic acid, stearic acid, oleic acid, and palmitic acid. After PEF treatment, the levels of total phenolics, total flavonoids, and oleuropein increased by 7.6%, 18.3% and 76%, respectively. There was no significant effect on the levels of 4 phenolic acids (vanillic acid, p-coumaric acid, ferulic acid and cinnamic acid), 2 lignans (lignans and apigenin), hydroxytyrosol, and 3 pigments (lutein, demagnetized chlorophyll, and carotenoids). In addition, PEF treatment significantly increased the content of tocopherols, with α, ß, γ, and δ tocopherols increasing by 9.8%, 10.7%, 13.6% and 38.4%, respectively. The free radical scavenging ability of DPPH and ABTS was also improved. In conclusion, the use of PEF significantly increased the yield of VOO oil as well as the levels of total phenolics, total flavonoids, oleuropein, tocopherol, and in vitro antioxidant activity.

Association of Triglyceride Glucose-Derived Indexes with Recurrent Events Following Atherosclerotic Cardiovascular Disease.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indexes of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indexes shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion: This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

Arbuscular mycorrhiza and plant growth promoting endophytes facilitates accumulation of saponin under moderate drought stress.

Objective: Paris polyphylla var. yunnanensis, one of the important medicinal plant resources in Yunnan, China, usually takes 6-8 years to be harvested. Therefore, it is urgent to find a method that can not only shorten its growth years, but also improve its quality. In this study, we examined the effects of a combination treatment of arbuscular mycorrhizal fungi (AMF) and plant growth-promoting endophytes (PGPE) and drought stress on the accumulation of saponins in it. Methods: P. polyphylla var. yunnanensis was infected with a mixture of AMF and PGPE under drought stress. The content of saponins, as well as morphological, physiological, and biochemical indicators, were all measured. The UGTs gene related to saponin synthesis was obtained from transcriptome data by homologous comparison, which were used for RT-PCR and phylogenetic analysis. Results: Regardless of water, AMF treatment could infect the roots of P. polyphylla var. yunnanensis, however double inoculation with AMF and PGPE (AMF + PGPE) would reduce the infection rate of AMF. Plant height, aboveground and underground fresh weight did not differ significantly between the single inoculation AMF and the double inoculation treatment under different water conditions, but the inoculation treatment significantly increased the plant height of P. polyphylla var. yunnanensis compared to the non-inoculation treatment. Single inoculation with AMF considerably increased the net photosynthetic rate, stomatal conductance, and transpiration rate of P. polyphylla var. yunnanensis leaves under various water conditions, but double inoculation with AMF + PGPE greatly increased the intercellular CO2 concentration and chlorophyll fluorescence parameter (Fv/Fm). Under diverse water treatments, single inoculation AMF had the highest proline content, whereas double inoculation AMF + PGPE may greatly improve the amount of abscisic acid (ABA) and indoleacetic acid (IAA) compared to normal water under moderate drought. Double inoculation AMF + PGPE treatment improved the proportion of N, P, and K in the rhizome of P. polyphylla var. yunnanensis under various water conditions. Under moderate drought stress, AMF + PGPE significantly enhanced the contents of P. polyphylla var. yunnanensis saponins I, II, VII, and total saponins as compared to normal water circumstances. Farnesyl diphosphate synthase (FPPS), Geranyl pyrophosphate synthase (GPPS), Cycloartenol synthase (CAS), and Squalene epoxidase (SE1) were the genes that were significantly up-regulated at the same time. The amount of saponins was favorably linked with the expression of CAS, GPPS, and SE1. Saponin VI content and glycosyl transferase (UGT) 010922 gene expression were found to be substantially associated, as was saponin II content and UGT010935 gene expression. Conclusion: Under moderate drought, AMF + PGPE was more conducive to the increase of hormone content, nutrient absorption, and total saponin content in P. polyphylla var. yunnanensis, and AMF + PGPE could up regulate the expression of key genes and UGTs genes in one or more steroidal saponin synthesis pathways to varying degrees, thereby stimulating the synthesis and accumulation of steroidal saponins in the rhizome of P. polyphylla var. yunnanensis. The combination of AMF and PGPE inoculation, as well as adequate soil drought, reduced the buildup of saponins in P. polyphylla var. yunnanensis and increased its quality.

Impact of perinatal factors on meconium aspiration syndrome in full-term newborns and the construction of a column chart prediction model: An observational study.

To explore the influence of perinatal-related factors on meconium aspiration syndrome (MAS) in full-term neonates and construct a nomogram prediction model for risk stratification of neonatal MAS and adoption of preventive measures. A total of 424 newborns and their mothers who were regularly examined at our hospital between January 2020 and December 2023 who had meconium-contaminated amniotic fluid during delivery were retrospectively selected as participants. Neonates were divided into MAS and non-MAS groups based on whether MAS occurred within 3 days after birth. Data from the 2 groups were analyzed, and factors influencing MAS were screened using multivariate logistic regression analysis. The R3.4.3 software was used to construct a nomogram prediction model for neonatal MAS risk. Receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the performance of the model, and its clinical effectiveness was evaluated using a decision curve. Among the 424 neonates with meconium-stained amniotic fluid, 51 developed MAS within 3 days of birth (12.03%). Multivariate logistic regression analysis showed that a low amniotic fluid index before delivery (OR = 2.862, P = .019), advanced gestational age (OR = 0.526, P = .034), cesarean section (OR = 2.650, P = .013), severe amniotic fluid contamination (OR = 4.199, P = .002), low umbilical cord blood pH (OR = 2.938, P = .011), and low neonatal Apgar 1-min score (OR = 3.133, P = .006) were influencing factors of MAS in full-term neonates. Based on the above indicators, a nomogram prediction model for MAS risk of full-term newborns was constructed. The area under the ROC curve of the model was 0.931. The model was also tested for goodness-of-fit deviation (χ2 = 3.465, P = .903). Decision curve analysis found that the model was clinically effective in predicting the net benefit of MAS risk in neonates with meconium-stained amniotic fluid. The construction of a column chart prediction model for neonatal MAS risk based on prenatal amniotic fluid index, gestational age, delivery method, amniotic fluid contamination level, newborn umbilical blood pH value, and Apgar 1-min score has a certain application value.

Inorganic Composition Modulation of Solid Electrolyte Interphase for Fast Charging Lithium Metal Batteries.

The solid electrolyte interphase (SEI) with lithium fluoride (LiF) is critical to the performance of lithium metal batteries (LMBs) due to its high stability and mechanical properties. However, the low Li ion conductivity of LiF impedes the rapid diffusion of Li ions in the SEI, which leads to localized Li ion oversaturation dendritic deposition and hinders the practical applications of LMBs at high-current regions (>3 C). To address this issue, a fluorophosphated SEI rich with fast ion-diffusing inorganic grain boundaries (LiF/Li3P) is introduced. By utilizing a sol electrolyte that contains highly dispersed porous LiF nanoparticles modified with phosphorus-containing functional groups, a fluorophosphated SEI is constructed and the presence of electrochemically active Li within these fast ion-diffusing grain boundaries (GBs-Li) that are non-nucleated is demonstrated, ensuring the stability of the Li || NCM811 cell for over 1000 cycles at fast-charging rates of 5 C (11 mA cm-2). Additionally, a practical, long cycling, and intrinsically safe LMB pouch cell with high energy density (400 Wh kg-1) is fabricated. The work reveals how SEI components and structure design can enable fast-charging LMBs.

Mesenchymal stem cells and their derived exosomes for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection typically presents with fever and respiratory symptoms, which can progress to severe respiratory distress syndrome and multiple organ failure. In severe cases, these complications may even lead to death. One of the causes of COVID-19 deaths is the cytokine storm caused by an overactive immune response. Therefore, suppressing the overactive immune response may be an effective strategy for treating COVID-19. Mesenchymal stem cells (MSCs) and their derived exosomes (MSCs-Exo) have potent homing abilities, immunomodulatory functions, regenerative repair, and antifibrotic effects, promising an effective tool in treating COVID-19. In this paper, we review the main mechanisms and potential roles of MSCs and MSCs-Exo in treating COVID-19. We also summarize relevant recent clinical trials, including the source of cells, the dosage and the efficacy, and the clinical value and problems in this field, providing more theoretical references for the clinical use of MSCs and MSCs-Exo in the treatment of COVID-19.

Visualization and Quantification of Drug Release by GSH-Responsive Multimodal Integrated Micelles.

Using molecular imaging techniques to monitor biomarkers and drug release profiles simultaneously is highly advantageous for cancer diagnosis and treatment. However, achieving the accurate quantification of both biomarkers and drug release with a single imaging modality is challenging. This study presents the development of a glutathione (GSH)-responsive polymer-based micelle, PEG-SS-FCy7/PEG-SS-GEM (PSFG), which can precisely localize the tumor using bimodal imaging and prevent drug leakage. These PSFG micelles exhibit a small particle size of 106.3 ± 12.7 nm with a uniform size distribution, and the drug loading efficiency can also be easily controlled by changing the PEG-SS-FCy7 (PSF) and PEG-SS-GEM (PSG) feeding ratio. The PSFG micelles display weak fluorescence emission and minimal drug release under physiological conditions but collapse in the presence of GSH to trigger near-infrared fluorescence and the 19F magnetic resonance imaging signal, allowing for real-time monitoring of intracellular GSH levels and drug release. GSH could synergistically promote the disassembly of the micellar structure, resulting in accelerated probe and drug release of up to about 93.1% after 24 h. These prodrug micelles exhibit high in vitro and in vivo antitumor abilities with minimal side effects. The GSH-responsive drug delivery system with dual-modal imaging capability provides a promising imaging-guided chemotherapeutic platform to probe the tumor microenvironment and quantify real-time drug release profiles with minimal side effects.

Low repetition rate 915†nm figure-9 ultrafast laser with all-fiber structure.

The advent of optical metrology applications has necessitated the development of compact, reliable, and cost-effective picosecond lasers operating around 900 nm, specifically catering to the requirements of precise ranging. In response to this demand, our work introduces an innovative solution-an all-fiber, all-polarization-maintaining (PM) figure-9 mode-locked laser operating at 915 nm. The proposed figure-9 Nd-doped fiber laser has a 69.2 m long cavity length, strategically designed and optimized to yield pulses with a combination of high pulse energy and low repetition rate. The laser can generate 915 nm laser pulses with a pulse energy of 4.65 nJ, a pulse duration of 15.2 ps under the repetition rate of 3.05 MHz. The 1064 nm amplified spontaneous emission (ASE) is deliberately filtered out, in order to prevent parasitic lasing and increase the spectral proportion of the 915 nm laser. The all-PM fiber configuration of this laser imparts exceptional mode-locking performance and environmental robustness, which is confirmed by long-term output power and spectral stability test. This compact and long-term reliable fiber laser could be a promising light source for applications like inter-satellite ranging.

Efficient word segmentation is preserved in older adult readers: Evidence from eye movements during Chinese reading.

College-aged readers use efficient strategies to segment and recognize words in naturally unspaced Chinese text. Whether this capability changes across the adult lifespan is unknown, although segmenting words in unspaced text may be challenging for older readers due to visual and cognitive declines in older age, including poorer parafoveal processing of upcoming characters. Accordingly, we conducted two eye movement experiments to test for age differences in word segmentation, each with 48 young (18-30 years) and 36 older (65+ years) native Chinese readers. Following Zhou and Li (2021), we focused on the processing of "incremental" three-character words, like (meaning "kindergartens"), which contain an embedded two-character word (e.g., , meaning "children"). In Experiment 1, either the three-character word or its embedded word was presented as the target word in sentence contexts where the three-character word always was plausible, and the embedded word was either plausible or implausible. Both age groups produced similar plausibility effects, suggesting age constancy in accessing the embedded word early during ambiguity processing before ultimately assigning an incremental word analysis. Experiment 2 provided further evidence that both younger and older readers access the embedded word early during ambiguity processing, but rapidly select the appropriate (incremental) word. Crucially, the findings suggest that word segmentation strategies do not differ with age. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Improvement of processable properties of plant-based high internal phase emulsions by mung bean protein isolate based on pH shift treatment.

BACKGROUND: High internal phase emulsions (HIPEs) are unique emulsion systems that transform liquid oil into solid-like fats, thus avoiding the use of saturated fat and leading to a healthier and more sustainable food system for consumers. HIPEs with oil volume fraction (ϕ) of 75-85% were fabricated with mung bean protein isolate (MPI) under different pH shift treatments at 1.0% concentration through the one-step method. In the present study, we investigated the physical properties, microstructures, processing properties, storage stability and rheological properties of HIPEs. RESULTS: The results suggested that the properties of MPI under different pH shift treatments were improved to different degrees, stabilizing HIPEs (ϕ = 75-85%) with various processability to meet food processing needs. Under alkali shift treatment conditions, the particle size of MPI was significantly reduced with better solubility. Moreover, the exposure of hydrophobic groups increased the surface hydrophobicity of MPI, awarding MPI better emulsifying properties, which could stabilize the HIPEs with higher oil phase fraction. In addition, the MPI under pH 12 shift treatment (MPI-12) had the best oil-carrying ability to form the stable HIPEs with oil volume fraction (ϕ) up to 85%, which was the highest oil phase in preparing the HIPEs using plant protein solely at a low concentration under neutral conditions. CONCLUSION: A series of stable HIPEs with different processing properties was simply and feasibly fabricated and these are of great potential in applying edible HIPEs. © 2024 Society of Chemical Industry.

S-acylation of YKT61 modulates its unconventional participation in the formation of SNARE complexes in Arabidopsis.

Hetero-tetrameric soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) complexes are critical for vesicle-target membrane fusion within the endomembrane system of eukaryotic cells. SNARE assembly involves four different SNARE motifs, Qa, Qb, Qc, and R, provided by three or four SNARE proteins. YKT6 is an atypical R-SNARE that lacks a transmembrane domain and is involved in multiple vesicle-target membrane fusions. Although YKT6 is evolutionarily conserved and essential, its function and regulation in different phyla seem distinct. Arabidopsis YKT61, the yeast and metazoan YKT6 homolog, is essential for gametophytic development, plays a critical role in sporophytic cells, and mediates multiple vesicle-target membrane fusion. However, its molecular regulation is unclear. We report here that YKT61 is S-acylated. Abolishing its S-acylation by a C195S mutation dissociates YKT61 from endomembrane structures and causes its functional loss. Although interacting with various SNARE proteins, YKT61 functions not as a canonical R-SNARE but coordinates with other R-SNAREs to participates in the formation of SNARE complexes. Phylum-specific molecular regulation of YKT6 may be evolved to allow more efficient SNARE-assembly in different eukaryotic cells.

Joint Association of Lipoprotein(a) and a Family History of Coronary Artery Disease with the Cardiovascular Outcomes in Patients with Chronic Coronary Syndrome.

AIM: No data are currently available regarding the association between Lp(a) and the cardiovascular outcomes in patients with coronary artery disease (CAD) according to their family history (FHx) of CAD. This study aimed to evaluate the significance of Lp(a) in predicting major adverse cardiovascular events (MACEs) in patients with chronic coronary syndrome (CCS) with or without FHx. METHODS: A total of 6056 patients with CCS were enrolled. Information on FHx was collected, and the plasma Lp(a) levels were measured. All patients were followed up regularly. The independent and joint associations of Lp(a) and FHx with the risk of MACEs, including cardiovascular death, nonfatal myocardial infarction, and stroke, were analyzed. RESULTS: With over an average of 50.35±18.58 months follow-up, 378 MACEs were recorded. A Cox regression analysis showed an elevated Lp(a) level to be an independent predictor for MACEs in patients with [hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.38-5.54] or without FHx (HR: 1.35, 95% CI: 1.02-1.77). In comparison to subjects with non-elevated Lp(a) and negative FHx, patients with elevated Lp(a) alone were at a nominally higher risk of MACEs (HR: 1.26, 95% CI: 0.96-1.67), while those with both had the highest risk (HR: 1.93, 95% CI: 1.14-3.28). Moreover, adding Lp(a) to the original model increased the C-statistic by 0.048 in subjects with FHx (p=0.004) and by 0.004 in those without FHx (p=0.391). CONCLUSIONS: The present study is the first to suggest that Lp(a) could be used to predict MACEs in CCS patients with or without FHx; however, its prognostic significance was more noteworthy in patients with FHx.

Can botulinum toxin injection alleviate the pain of bruxism? A Bayesian network analysis and a single-arm analysis.

Background/purpose: There is inconsistent evidence regarding whether the botulinum toxin A (BTA) injection can relieve pain caused by bruxism. This study aimed to estimate the efficiency of BTA injection in relieving pain caused by bruxism at different follow-up periods. Materials and methods: Five electronic databases were searched from 2005 to 2022 using search terms related to botulinum toxin and bruxism. Only controlled clinical trials were included. Two investigators reviewed each article and discussed any disagreements until a consensus was reached. Pain outcomes as evaluated by the visual analogue scale (VAS) were subjected to single-arm and Bayesian network meta-analyses. Pooling data were measured by a random-effects model. Results: Eleven studies with a total of 365 bruxism patients were included. According to the single-arm analyses of the pooled data, the reduction in bruxism-related pain after BTA injection measured 4.06 points (95% CI = 3.37 to 4.75) on the VAS, and the pain relief was significant in the first 6 months after treatment (P < 0.01). According to the Bayesian analysis, BTA also resulted in significantly greater pain relief than oral splinting (mean difference (MD), -1.5; 95% credible interval (CrI) = -2.7 to -0.19) or saline injection (MD, -3.3; 95% CrI = -6.2 to -0.32). Conclusion: BTA significantly relieves the pain of bruxism for 6 months after injection, and its therapeutic efficacy was higher than that of oral splinting. Nevertheless, further long-term follow-up randomized controlled trials comparing BTA with other management or drugs are warranted.

Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism.

Age-related changes in testicular function can impact health and well-being. The mechanisms underlying age-related testicular dysfunction, such as late-onset hypogonadism (LOH), remain incompletely understood. Using single-cell RNA sequencing on human testes with LOH, we delineated Sertoli cells (SCs) as pivotal metabolic coordinators within the testicular microenvironment. In particular, lysosomal acidity probing revealed compromised degradative capacity in aged SCs, hindering autophagy and phagocytic flux. Consequently, SCs accumulated metabolites, including cholesterol, and have increased inflammatory gene expression; thus, we termed these cells as phago-/auto-lysosomal deregulated SCs. Exposure to a high-fat diet-induced phago-/auto-lysosomal dysregulated-like SCs, recapitulating LOH features in mice. Notably, efferent ductular injection and systemic TRPML1 agonist administration restored lysosomal function, normalizing testosterone deficiency and associated abnormalities in high-fat diet-induced LOH mice. Our findings underscore the central role of SCs in testis aging, presenting a promising therapeutic avenue for LOH.