Prediction of prognosis in supramalleolar osteotomy with or without additional fibula osteotomy by approaching a biomechanical study: a finite element analysis.

Supramalleolar osteotomy (SMO) is a representative procedure to restore a malalignment in the varus ankle deformity by shifting the concentrated pressure on the medial ankle joint to the lateral area. Additionally, fibula osteotomy (FO) is selectively selected and performed according to the surgeon's preference. However, it is controversial whether FO is effective in shifting the abnormal pressure from the medial to the lateral area on the ankle joint. Some cadaveric studies have been performed to prove this. However, it is difficult to consistently reconstruct amount of the varus ankle deformities angle in cadavers and to guarantee reliable contact pressure between the ankle joint. Thus, the aim of this study was predicted and quantitatively compared a peak pressure between single SMO and SMO with FO procedure by using a finite element analysis as a powerful biomechanical tool to those limitations of cadaveric study. This study reconstructed total 4 3D foot and ankle models including a normal and pre-op model and 2 post-op models. The pre-op model was modified by assigning 10° varus tilting corresponding to stage 3b in the classification of varus ankle osteoarthritis based on the validated normal model. Also, the post-op models were reconstructed by applying single SMO and SMO with FO, respectively. All of the models were assumed as one-leg standing position and to mimic smooth ankle joint motion. Peak contact pressure change was predicted at the medial ankle joint by using computational simulation. As a result, 2 post-op models showed a remarkably peak pressure reduction by up to 5.5 times on the medial tibiotalar joint. However, a comparison between single SMO and SMO with FO model showed no appreciable differences. In conclusion, this study predicted that single SMO may be as effective as SMO with FO in reducing peak contact pressure on the medial tibiotalar joint in varus ankle osteoarthritis.

Nitrogen-Doped Carbon Dots: A New Powerful Fluorescent Dye with Substantial Effect on Bacterial Cell Labeling.

Carbon dots (CDs)-minute carbon nanoparticles with remarkable luminescent properties, photostability, and low toxicity-show potential for various applications. CDs synthesized using citric acid and urea are the least toxic to biological environments. Here, we aimed to explore the effect of CDs synthesized using citric acid and urea at 50, 33, and 25% (CDs 1/1, 1/2, and 1/3, respectively) weight ratios in a microwave on bacterial cell fluorescence sensing and labeling. The nanoscale properties of CDs were investigated via transmission electron microscopy and dynamic light scattering particle size analysis. X-ray powder diffraction confirmed the graphitic structures of CDs. X-ray photoelectron spectroscopy revealed that the nitrogen content increased gradually with increasing urea ratios, indicating functional group changes. Transient photoluminescence decay periods demonstrated superior fluorescence intensity of CDs 1/3 under blue, green, and red lights. The use of CDs was notably more efficient than traditional methods in staining bacterial cells. Fluorescence microscopy of 10 g-positive and 10 g-negative bacteria revealed enhanced staining of Gram-positive strains, with CDs 1/3 presenting the best results. The CDs exhibited excellent photostability, maintaining poststaining fluorescence for 100 min, surpassing the performance of conventional dyes. CDs could serve as potential fluorescent dyes for the rapid discrimination of Gram-positive and Gram-negative bacteria.

Physics-driven unsupervised deep learning network for programmable metasurface-based beamforming.

Programmable metasurfaces have garnered significant attention for their capacity to dynamically manipulate electromagnetic (EM) waves. In particular, the programmable metasurfaces offer to generate a wide range of EM beams when the appropriate digital coding patterns are designed. Traditionally, optimizing the coding patterns involves time-consuming nonlinear optimization algorithms due to the high computational complexity. In this study, we propose a physics-assisted deep learning (DL) model that can calculate the coding pattern in milliseconds, requiring only a simple depiction of the desired beam. An extended version of the macroscopic model for digital coding metasurface is introduced as the physics-driven component, which can compute the radiation pattern rapidly based on the provided coding pattern. The integration of the macroscopic model ensures to generate the physics-compliant coding designs. We validate the proposed method experimentally by measuring several coding patterns for both single-beam and dual-beam scenarios, which demonstrate good performance of beamforming.

Four novel species of Pleurotheciaceae collected from freshwater habitats in Jiangxi Province, China.

During an investigation of fungal diversity from freshwater environments in different regions in Jiangxi Province, China, four interesting species were collected. Morphology coupled with combined gene analysis of an ITS, LSU, SSU, and rpb2 DNA sequence data showed that they belong to the family Pleurotheciaceae. Four new species, Pleurotheciella ganzhouensis, Pla. irregularis, Pla. verrucosa, and Pleurothecium jiangxiense are herein described. Pleurotheciella ganzhouensis is characterized by its capsule-shaped conidia and short conidiophores, while Pla. irregularis has amorphous conidiophores and 3-septate conidia. Pleurotheciella verrucosa has cylindrical or verrucolose conidiogenous cells, 1-septate, narrowly fusiform, meniscus or subclavate conidia. Pleurothecium jiangxiense characterized in having conidiogenous cells with dense cylindrical denticles and short conidiophores. Pleurothecium obovoideum was transferred to Neomonodictys based on phylogenetic evidence. All species are compared with other similar species and comprehensive descriptions, micrographs, and phylogenetic data are provided.

Association of sleep patterns and disorders with metabolic dysfunction-associated steatotic liver disease and liver fibrosis in contemporary American adults.

INTRODUCTION AND OBJECTIVES: The impact of sleep on metabolic dysfunction-associated steatotic liver disease (MASLD) in American adults remains unclear. This study aimed to address the relationship of sleep patterns and disorders with MASLD and liver fibrosis comprehensively. MATERIALS AND METHODS: This cross-sectional study included adult participants from the National Health and Nutrition Examination Survey 2017-2020. Multivariate adjusted regression analysis were used to examine the association of sleep with MASLD and liver fibrosis. We further addressed these associations using restricted cubic splines, mediation analysis, stratified analysis and multiple sensitivity analysis. RESULTS: We enrolled 5368 participants. Certain sleep disorders, sleep duration, high sleep debt and specific sleep-wake time were associated with MASLD. Late workday sleep was a shared risk factor for MASLD and liver fibrosis. Short sleep on workdays and free days favored MASLD, whereas average weekly long sleep protected against MASLD. Workday, free day and average weekly optimal sleep duration was 7.5 h, 8 h and 7.78 h, respectively. Mediation analysis suggested that fasting glucose and high-density lipoprotein cholesterol indirectly mediated the relationship between sleep duration and MASLD, whereas stratified analysis showed that sex influenced the relationship, and that the correlation was only observed in women and specific age groups. CONCLUSIONS: Sleep duration independently affected MASLD but only in women and specific age groups. Moreover, late sleep on workdays was a shared risk factor for MASLD and liver fibrosis. These results suggest targeting sleep behaviors for MASLD prevention and developing age- and sex-specific strategies.

Magnetic resonance imaging-based radiomics model for preoperative assessment of risk stratification in endometrial cancer.

BACKGROUND: Preoperative risk stratification is significant for the management of endometrial cancer (EC) patients. Radiomics based on magnetic resonance imaging (MRI) in combination with clinical features may be useful to predict the risk grade of EC. AIM: To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI. METHODS: The study comprised 112 EC patients. The participants were randomly separated into training and validation groups with a 7:3 ratio. Logistic regression analysis was applied to uncover independent clinical predictors. These predictors were then used to create a clinical nomogram. Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images, the Mann-Whitney U test, Pearson test, and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features, which were subsequently utilized to generate a radiomic signature. Seven machine learning strategies were used to construct radiomic models that relied on the screening features. The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators. RESULTS: Having an accuracy of 0.82 along with an area under the curve (AUC) of 0.915 [95% confidence interval (CI): 0.806-0.986], the random forest method trained on radiomics characteristics performed better than expected. The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram (AUC: 0.75, 95%CI: 0.611-0.899) and the combined nomogram (AUC: 0.869, 95%CI: 0.702-0.986) that integrated clinical parameters and radiomic signature. CONCLUSION: The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

Mesenchymal stem cell therapy for liver fibrosis need "partner": Results based on a meta-analysis of preclinical studies.

BACKGROUND: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been demonstrated in several clinical studies. However, their low survival and liver implantation rates remain problematic. In recent years, a large number of studies in animal models of liver fibrosis have shown that MSCs combined with drugs can improve the efficacy of MSCs in the treatment of liver fibrosis alone and inhibit its progression to end-stage liver disease. This has inspired new ways of thinking about treating liver fibrosis. AIM: To investigate the effectiveness and mechanisms of MSCs combined with drugs in treating liver fibrosis. METHODS: Data sources included four electronic databases and were constructed until January 2024. The subjects, interventions, comparators, outcomes, and study design principle were used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Relevant randomised controlled trials were selected, and the final 13 studies were included in the final study. RESULTS: A total of 13 studies were included after screening. Pooled analysis showed that MSCs combined with drug therapy significantly improved liver function, promoted the repair of damaged liver tissues, reduced the level of liver fibrosis-related indexes, and effectively ameliorated hepatic fibrosis by modulating the hepatic inflammatory microenvironment, promoting the homing of MSCs, and regulating the relevant signaling pathways, and the treatment efficacy was superior to MSCs alone. However, the combined treatment statistics showed no ame-lioration in serum albumin levels (standardized mean difference = 0.77, 95% confidence interval: -0.13 to 1.68, P = 0.09). CONCLUSION: In conclusion, MSCs combined with drugs for treating liver fibrosis effectively make up for the shortcomings of MSCs in their therapeutic effects. However, due to the different drugs, the treatment mechanism and effect also differ. Therefore, more randomized controlled trials are needed to compare the therapeutic efficacy of different drugs in combination with MSCs, aiming to select the "best companion" of MSCs in treating hepatic fibrosis.

Fine-tuning of IPA1 transactivation activity by E3 ligase IPI7-mediated non-proteolytic K29-ubiquitination during Magnaporthe oryzae infection.

The Ideal Plant Architecture 1 (IPA1) transcription factor promotes rice yield and immunity through phosphorylation at its amino acid residue Ser163 as a switch. Although phosphorylated IPA1 mimic, IPA1(S163D), directly targets the promoter of immune response gene WRKY45, it cannot activate its expression. Here, we identified a co-activator of IPA1(S163D), a RING-finger E3 ligase IPA1 interactor 7 (IPI7), which fine-tunes the transcriptional activity of IPA1 to timely promote plant immunity and simultaneously maintain growth for yield. IPI7 interacts with IPA1 and promotes K29-polyubiquitination of IPA1 in vitro and in vivo. However, the stability of IPA1 protein is not affected by IPI7-mediated ubiquitination. The IPI7-promoted K29-polyubiquitination of IPA1 is induced by Magnaporthe oryzae infection and required for phosphorylated IPA1 to transactivate WRKY45 expression for immune response but not for plain IPA1 to transactivate DENSE AND ERECT PANICLES 1 (DEP1) expression for panicle development. IPI7 knockout impairs IPA1-mediated immunity but not yield. Our study reveals that plants utilize non-proteolytic K29-ubiquitination as a response to pathogen infection to fine-tune IPA1 transactivation activity for promoting immunity.

Directed crystalline symmetry transformation of blue-phase liquid crystals by reverse electrostriction.

Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials.

Interaction of phosphorus and GA3 improved oilseed flax grain yield and phosphorus-utilization efficiency.

Introduction: Phosphorus nutrition and hormone concentration both affect crop yield formation. Ascertaining the interaction of phosphorus and GA3 has a synergistic effect on the grain yield and phosphorus utilization efficiency of oilseed flax in dryland. It is extremely important for improving grain yield and phosphorus utilization efficiency. Methods: A field experiment was conducted in 2019 and 2020 at the Dingxi Oil Crops Test Station to investigated the effects of phosphorus, gibberellin (GA3), and their interaction on the grain yield and phosphorus-utilization efficiency of oilseed flax plants. Phosphorus fertilizer was applied at three levels (0, 67.5, 135 kg P2O5·ha-1) and GA3 was also sprayed at three concentrations (0, 15, and 30 mg·L-1). Results: The results showed that application of 67.5 kg P2O5·ha-1 reduced leaves acid phosphatase (ACPase) activity, but increased phosphorus accumulation throughout the growth period, the 1000-kernel weight (TKW), and the number of grains per capsule. Spraying GA3 significantly increased the leaves ACPase activity, phosphorus accumulation after anthesis and its contribution to grain, phosphorus-utilization efficiency, the number of capsules per plant, and TKW. The phosphorus accumulation at the anthesis, kernel, and maturity stages under the treatment of fertilizing 67.5 kg P2O5·ha-1 and spraying 30 mg·L-1 GA3 were increased by 56.06%, 73.51%, and 62.17%, respectively, compared with the control (no phosphorus, no GA3). And the phosphorus accumulation after anthesis and its contribution to grain also increased. 67.5 kg P2O5·ha-1 combined with 30 mg·L-1 GA3 and 135 kg P2O5·ha-1 combined with 15 mg·L-1 GA3 both significantly increased grain yield of oilseed flax, reaching 1696 kg·ha-1 and 1716 kg·ha-1 across two years, respectively. And there was no significant difference between them. However, the former treatment significant increased the apparent utilization rate, agronomic utilization rate, and partial productivity of phosphorus. The interaction between phosphorus and GA3 was significant for grain yield. Conclusion: Therefore, the application of 67.5 kg P2O5·ha-1 in combination with 30 mg·L-1 GA3 is an effective fertilization approach for enhancing oilseed flax growth and grain yield in the experiment region and other similar areas.

Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS).

Background: Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use. Objective: To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference. Methods: FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals. Results: Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%). Conclusion: Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use.

Structural and Mutational Analyses of Trehalose Synthase from Deinococcus radiodurans Reveal the Interconversion of Maltose-Trehalose Mechanism.

Trehalose synthase (TreS) catalyzes the reversible interconversion of maltose to trehalose, playing a vital role in trehalose production. Understanding the catalytic mechanism of TreS is crucial for optimizing the enzyme activity and enhancing its suitability for industrial applications. Here, we report the crystal structures of both the wild type and the E324D mutant of Deinococcus radiodurans trehalose synthase in complex with the trehalose analogue, validoxylamine A. By employing structure-guided mutagenesis, we identified N253, E320, and E324 as crucial residues within the +1 subsite for isomerase activity. Based on these complex structures, we propose the catalytic mechanism underlying the reversible interconversion of maltose to trehalose. These findings significantly advance our comprehension of the reaction mechanism of TreS.

Poly I: C Alleviated Duck Intestinal Injury Infected with Duck Viral Enteritis by Inhibiting Apoptosis.

Duck enteritis virus (DEV) may lead to vascular injury, gastrointestinal mucosal erosion, lymphoid organ injury, and Polyinosinic-polycytidylic acid (Poly I:C) has an antiviral effect by inducing low levels of interferon. The purpose of this study was to explore the pathogenesis of DEV-induced intestinal injury in ducks and to verify the therapeutic effects of different concentrations of Poly I:C. In this study, duck enteritis model was established by infecting healthy Pekin ducks with DEV. Duck intestinal tissues were extracted from normal control group, model group, and treatment group with different doses of Poly I:C. In vivo, HE and TUNEL staining were used to observe the morphological changes and apoptosis. In vitro, the proliferation and apoptosis of duck intestinal epithelial cells were evaluated by MTT assay, TUNEL staining, and flow cytometry. The results showed that Poly I:C protected ducks from DEV toxicity by improving intestinal morphology and inhibiting apoptosis. In addition, the antiviral effect of Poly I:C on DEV was found in a dose-dependent manner, with a more relatively obvious effect at a high dose of Poly I:C. All in all, these results demonstrated that Poly I:C played a vital role in the apoptosis induced by DEV in ducks and modest dose of Poly I:C treatment worked well and may provide important reference for the development of new antiviral drugs in the future.

Specially Structured AgCuTi Foil Enables High-Strength and Defect-Free Brazing of Sapphire and Ti6Al4V Alloys: The Microstructure and Fracture Characteristics.

A novel AgCuTi brazing foil with a unique microstructure was developed, which could achieve strong vacuum brazing of Ti6Al4V (TC4) and sapphire. The brazing foil was composed of Ag solid solution (Ag(s,s)), Cu solid solution (Cu(s,s)), and layered Ti-rich phases, and had a low liquidus temperature of 790 °C and a narrow melting range of 16 °C, facilitating the defect-free joining of TC4 and sapphire. The sapphire/TC4 joint fabricated by using this novel AgCuTi brazing foil exhibited an outstanding average shear strength of up to 132.2 MPa, which was the highest value ever reported. The sapphire/TC4 joint had a characteristic structure, featuring a brazing seam reinforced by TiCu particles and a thin Ti3(Cu,Al)3O reaction layer of about 1.3 µm. The fracture mechanism of the sapphire/TC4 joint was revealed. The crack originated at the brazing seam with TiCu particles, then propagated through the Ti3(Cu,Al)3O reaction layer, detached the reaction layer from the sapphire, and finally penetrated into the sapphire. This study offers valuable insights into the design of active brazing alloys and reliable metal-ceramic bonding.

The effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration.

The saline wastewater produced in industrial activities and seawater use would flow into wastewater treatment plants and affect the characteristic of extracellular polymeric substance (EPS) of activated sludge, which could potentially impact the removal of antibiotics via adsorption. Nonetheless, the effect of salinity on trimethoprim adsorption by activated sludge extracellular polymeric substances at trace concentration and the underlying mechanism remain largely unknown. In this study, the effect of salinity on the adsorption removal of a typical antibiotic, i.e., trimethoprim (TMP) at trace concentration (25.0 µg/L) was evaluated. The results showed the content of EPS was decreased significantly from 56.36 to 21.70 mg/g VSS when the salinity was increased from 0 to 10 g/L. Protein fractions occupied the predominant component of EPS, whose concentration was decreased from 38.17 to 12.83 mg/g VSS. The equilibrium adsorption capacity of activated sludge for TMP was decreased by 49.70% (from 4.97 to 2.50 µg/g VSS). The fluorescence quenching results indicated the fluorescence intensity of tryptophan-like substances was decreased by 30% and the adsorption sites of EPS were decreased from 0.51 to 0.21 when the salinity was increased. The infrared spectrum and XPS results showed that the nitrogen-containing groups from protein were decreased significantly. The circular dichroic analysis showed α helix structure of protein in EPS was decreased with the increase of salinity, which was responsible for the decrease of adsorption capacity for TMP.

The clinical value of applying diffusion-weighted imaging combined with T2-weighted imaging to assess diagnostic performance of muscularis propria invasion in mid-to-high rectal cancer.

PURPOSE: This study aimed to evaluate the diagnostic performance of combining diffusion-weighted imaging (DWI) with T2-weighted imaging (T2WI) for detecting muscularis propria invasion in rectal cancer. METHODS: We conducted a retrospective analysis of MR images from 76 patients with pathologically confirmed rectal cancer between January 2018 and June 2022. Patients were categorized into invasion and non-invasion groups. the present of muscularis propria invasion. The examination regimen included T2WI, dynamic enhanced scanning and DWI.The apparent diffusion coefficient (ADC) values from DWI were compared between the groups, and the diagnostic performance of combining ADC with T2WI was assessed. RESULTS: There were differences in ADCmean, ADCmsi, and ADCmin values between the non-invasion group and theinvasion group, and the t values were 3.949, 2.221 and 2.978, respectively. The P values were 0.000, 0.029 and 0.004, respectively. Using an ADCmean threshold of 1.07 × 10- 3 mm²/s, the sensitivity and specificity for detecting muscularis propria invasion were 82.22% and 61.29%, respectively, with an overall diagnostic accuracy of 89.5%. For ADCmsi, with a threshold of 0.996 × 10- 3 mm²/s, the sensitivity and specificity were 62.75% and 73.33%, respectively, yielding a diagnostic accuracy of 82.9%. The ADCmin, with a threshold of 0.854 × 10- 3 mm²/s, demonstrated sensitivity and specificity of 78.43% and 66.67%, respectively, with a diagnostic accuracy of 85.5%. CONCLUSION: T2WI combined ADC value has a good predictive value for judging the degree of musculature invasion of medium-to-high rectal cancer, while ADC mean has a higher comprehensive diagnostic efficiency. Our finding may provide reference for increasing accuracy in mid-to-high rectal cancer diagnosis.

[Changes in seminal plasma composition and corresponding sperm quality in patients with chronic prostatitis / chronic pelvic pain syndrome: Progress in studies].

Prostatitis is one of the three most common prostate diseases in men, the other two being prostatic hyperplasia and prostate cancer, and about 50% of men worldwide have been attacked by prostatitis during their lives. The incidence of infertility is significantly higher in patients with chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) than in those without it, which is mainly attributed to the changed semen composition of the CP/CPPS patients. Using the key words chronic prostatitis, chronic pelvic pain syndrome, sperm, semen, and seminal plasma, we searched PubMed and Medical Lines online for originals, review articles, clinical trials, case reports and associated citations on humans and animals published up to 2024. We comprehensively reviewed the previous studies and investigations relating chronic prostatitis, seminal plasma change and sperm quality, and discussed the impact of the change of semen composition on sperm quality.

Construction of Near-Infrared Probes with Remarkable Large Stokes Shift Based on a Novel Purine Platform for the Visualization of mtG4 Upregulation during Mitochondrial Disorder in Somatic Cells and Human Sperms.

G-quadruplex structures within the nuclear genome (nG4) is an important regulatory factor, while the function of G4 in the mitochondrial genome (mtG4) still needs to be explored, especially in human sperms. To gain a better understanding of the relationship between mtG4 and mitochondrial function, it is crucial to develop excellent probes that can selectively visualize and track mtG4 in both somatic cells and sperms. Herein, based on our previous research on purine frameworks, we attempted for the first time to extend the conjugated structure from the C-8 site of purine skeleton and discovered that the purine derivative modified by the C-8 aldehyde group is an ideal platform for constructing near-infrared probes with extremely large Stokes shift (>220 nm). Compared with the compound substituted with methylpyridine (PAP), the molecule substituted with methylthiazole orange (PATO) showed better G4 recognition ability, including longer emission (∼720 nm), more significant fluorescent enhancement (∼67-fold), lower background, and excellent photostability. PATO exhibited a sensitive response to mtG4 variation in both somatic cells and human sperms. Most importantly, PATO helped us to discover that mtG4 was significantly increased in cells with mitochondrial respiratory chain damage caused by complex I inhibitors (6-OHDA and rotenone), as well as in human sperms that suffer from oxidative stress. Altogether, our study not only provides a novel ideal molecular platform for constructing high-performance probes but also develops an effective tool for studying the relationship between mtG4 and mitochondrial function in both somatic cells and human sperms.

Asymmetric Organocatalytic 1,3-Dipolar Cycloaddition of Azomethine Ylides with ß-Substituted Cyclic Enones.

The enantioselective and diastereoselective control of 1,3-dipolar cycloaddition reactions to ß-substituted cyclic enones has been developed. The 1,3-dipolar cycloaddition of phthalazinium dicyanomethanides with cyclic dienones affords chiral tetrahydropyrrolo[2,1-a]phthalazine derivatives 3 through vinylogous iminium ion activation by combining a cinchona-based primary amine C3 and a chiral camphorsulfonic acid additive. Conversely, with a weaker 3,5-bis(trifluoromethyl)benzoic acid additive, the 1,3-dipolar cycloaddition of phthalazinium dicyanomethanides with ß-substituted cyclic enones leads to chiral hexahydroisoindolo[1,2-a]phthalazin-10(8H)-one derivatives 4 with excellent stereocontrol via endo-dienamine activation.

Comparing musculoskeletal and connective tissue disorder risks of teriparatide and abaloparatide in osteoporosis: an analysis based on FDA adverse event reporting system (FAERS).

BACKGROUND: Osteoporosis (OP), characterized by low bone mass and increased fracture risk, is a prevalent skeletal disorder. Teriparatide (TP) and abaloparatide (ABL) are anabolic agents that may reduce fracture incidence, but their impact on musculoskeletal and connective tissue disorders (MCTD) risk is uncertain. RESEARCH DESIGN AND METHODS: A retrospective, observational disproportionality analysis was conducted utilizing FAERS data from Q1 2004 to Q3 2023, where TP or ABL was identified as the primary suspect drug. Multiple data mining algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to detect MCTD safety signals. RESULTS: A total of 366,747 TP-related and 422,377 ABL-related cases were identified, predominantly among female patients aged ≥45 years. The top specific AEs involved musculoskeletal, connective tissue, and administration site disorders. Comparative analysis revealed a higher frequency of AEs related to the nervous, cardiovascular, and gastrointestinal systems for ABL compared to TP. Both drugs exhibited strong signals for arthralgia, limb pain, back pain, muscle spasms, bone pain, muscle pain, and muscle weakness. CONCLUSION: The analysis suggests a potential MCTD risk with TP and ABL treatment in OP patients, highlighting the need for AE monitoring and management in clinical practice. This contributes to a better understanding of the safety profiles of these anabolic medications.