Exploring near-infrared autofluorescence properties in parathyroid tissue: an analysis of fresh and paraffin-embedded thyroidectomy specimens.

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety. Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues. Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D. Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels. Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology.

Glutamine metabolism promotes human trophoblast cell invasion via COL1A1 mediated by PI3K-AKT pathway.

Abnormal trophoblast invasion function is an important cause of recurrent spontaneous abortion (RSA). Recent research has revealed a connection between glutamine metabolism and RSA. However, the interplay between these three factors and their related mechanisms remains unclear. To address this issue, we collected villus tissues from 10 healthy women with induced abortion and from 10 women with RSA to detect glutamine metabolism. Then, the trophoblast cell line HTR-8/SVneo was used in vitro to explore the effect of glutamine metabolism on trophoblast cells invasion, which was tested by transwell assay. We found that the concentration of glutamine in the villi of the normal pregnancy group was significantly higher than that in the RSA group. Correspondingly, the expression levels of key enzymes involved in glutamine synthesis and catabolism, including glutamine synthetase and glutaminase, were significantly higher in the villi of the normal pregnancy group. Regarding trophoblast cells, glutamine markedly enhanced the proliferative and invasive abilities of HTR-8/SVneo cells. Additionally, collagen type I alpha 1 (COL1A1) was confirmed to be a downstream target of glutamine, and glutamine also activated the PI3K-AKT pathway in HTR-8/SVneo cells. These findings indicate that glutamine metabolism facilitates the invasion of trophoblasts by up-regulating COL1A1 expression through the activation of the PI3K-AKT pathway, but the specific mechanism of COL1A1 requires further study.

Single-cell atlas of healthy vocal folds and cellular function in the endothelial-to-mesenchymal transition.

The vocal fold is an architecturally complex organ comprising a heterogeneous mixture of various layers of individual epithelial and mesenchymal cell lineages. Here we performed single-cell RNA sequencing profiling of 5836 cells from the vocal folds of adult Sprague-Dawley rats. Combined with immunostaining, we generated a spatial and transcriptional map of the vocal fold cells and characterized the subpopulations of epithelial cells, mesenchymal cells, endothelial cells, and immune cells. We also identified a novel epithelial-to-mesenchymal transition-associated epithelial cell subset that was mainly found in the basal epithelial layers. We further confirmed that this subset acts as intermediate cells with similar genetic features to epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma. Finally, we present the complex intracellular communication network involved homeostasis using CellChat analysis. These studies define the cellular and molecular framework of the biology and pathology of the VF mucosa and reveal the functional importance of developmental pathways in pathological states in cancer.

A Hypoxia-Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage.

The significance of hypoxia at the maternal-fetal interface is proven to be self-explanatory in the context of pregnancy. During the first trimester, low oxygen conditions play a crucial role in processes such as angiogenesis, trophoblast invasion and differentiation, and immune regulation. Recently, there has been increasing research on decidual macrophages, which contribute to the maintenance of immune tolerance, placental and fetal vascular development, and spiral artery remodeling, to investigate the effects of hypoxia on their biological behaviors. On these grounds, this review describes the dynamic changes in oxygen levels at the maternal-fetal interface throughout gestation, summarizing current knowledge on how the hypoxic environment sustains a successful pregnancy by regulating retention, differentiation and efferocytosis of decidual macrophages. Additionally, we explore the relationship between spontaneous miscarriages and an abnormal hypoxia-macrophage axis, shedding light on the underlying mechanisms. However, further studies are essential to elucidate these pathways in greater detail and to develop targeted interventions that could improve pregnancy outcomes.

Data-driven risk stratification and precision management of pulmonary nodules detected on chest computed tomography.

The widespread implementation of low-dose computed tomography (LDCT) in lung cancer screening has led to the increasing detection of pulmonary nodules. However, precisely evaluating the malignancy risk of pulmonary nodules remains a formidable challenge. Here we propose a triage-driven Chinese Lung Nodules Reporting and Data System (C-Lung-RADS) utilizing a medical checkup cohort of 45,064 cases. The system was operated in a stepwise fashion, initially distinguishing low-, mid-, high- and extremely high-risk nodules based on their size and density. Subsequently, it progressively integrated imaging information, demographic characteristics and follow-up data to pinpoint suspicious malignant nodules and refine the risk scale. The multidimensional system achieved a state-of-the-art performance with an area under the curve (AUC) of 0.918 (95% confidence interval (CI) 0.918-0.919) on the internal testing dataset, outperforming the single-dimensional approach (AUC of 0.881, 95% CI 0.880-0.882). Moreover, C-Lung-RADS exhibited a superior sensitivity compared with Lung-RADS v2022 (87.1% versus 63.3%) in an independent cohort, which was screened using mobile computed tomography scanners to broaden screening accessibility in resource-constrained settings. With its foundation in precise risk stratification and tailored management, this system has minimized unnecessary invasive procedures for low-risk cases and recommended prompt intervention for extremely high-risk nodules to avert diagnostic delays. This approach has the potential to enhance the decision-making paradigm and facilitate a more efficient diagnosis of lung cancer during routine checkups as well as screening scenarios.

Detailed analysis of learning phases and outcomes in robotic and endoscopic thyroidectomy.

BACKGROUND: Thyroid surgery has undergone significant transformation with the introduction of minimally invasive techniques, particularly robotic and endoscopic thyroidectomy. These advancements offer improved precision and faster recovery but also present unique challenges. This study aims to compare the learning curves, operational efficiencies, and patient outcomes of robotic versus endoscopic thyroidectomy. METHODS: A retrospective cohort study was conducted, analyzing 258 robotic (da Vinci) and 214 endoscopic thyroidectomy cases. Key metrics such as operation duration, drainage volume, lymph node dissection outcomes, and hypoparathyroidism incidence were assessed to understand surgical learning curves and efficiency. RESULTS: Robotic thyroidectomy showed a longer learning curve with initially longer operation times and higher drainage volumes but superior lymph node dissection outcomes. Both techniques were safe, with no permanent hypoparathyroidism or recurrent laryngeal nerve damage reported. The study delineated four distinct stages in the robotic and endoscopic surgery learning curve, each marked by specific improvements in proficiency. Endoscopic thyroidectomy displayed a shorter learning curve, leading to quicker operational efficiency gains. CONCLUSION: Robotic and endoscopic thyroidectomies are viable minimally invasive approaches, each with its learning curves and efficiency metrics. Despite initial challenges and a longer learning period for robotic surgery, its benefits in complex dissections may justify specialized training. Structured training programs tailored to each technique are crucial for improving outcomes and efficiency. Future research should focus on optimizing training protocols and increasing accessibility to these technologies, enhancing patient care in thyroid surgery.

Mechanism of Panax notoginseng saponins modulation of miR-214-3p/NR1I3 affecting the pharmacodynamics and pharmacokinetics of warfarin.

Background: With the prevalence of dietary supplements, the use of combinations of herbs and drugs is gradually increasing, together with the risk of drug interactions. In our clinical work, we unexpectedly found that the combination of Panax notoginseng and warfarin, which are herbs that activate blood circulation and remove blood stasis, showed antagonistic effects instead. The purpose of this study was to evaluate the drug interaction between Panax notoginseng saponins (PNS) and warfarin, the main active ingredient of Panax notoginseng, and to explore the interaction mechanism. Methods: The effects and mechanisms of PNS on the pharmacodynamics and pharmacokinetics of warfarin were explored mainly in Sprague-Dawley rats and HepG2 cells. Elisa was used to detect the concentrations of coagulation factors, HPLC-MS to detect the blood concentrations of warfarin in rats, immunoblotting was employed to examine protein levels, qRT-PCR to detect mRNA levels, cellular immunofluorescence to detect the localization of NR1I3, and dual luciferase to verify the binding of miR-214-3p and NR1I3. Results: PNS significantly accelerated warfarin metabolism and reduced its efficacy, accompanied by increased expression of NR1I3 and CYP2C9. Interference with NR1I3 rescued the accelerated metabolism of warfarin induce by PNS co-administration. In addition, we demonstrated that PNS significantly reduced miR-214-3p expression, whereas miR-214-3p overexpression reduced NR1I3 and CYP2C9 expression, resulting in a weakened antagonistic effect of PNS on warfarin. Additionally, we found that miR-214-3p bound directly to NR1I3 3'-UTR and significantly downregulated NR1I3 expression. Conclusion: Our study demonstrated that PNS accelerates warfarin metabolism and reduces its pharmacodynamics by downregulating miR-214-3p, leading to increased expression of its target gene NR1I3, these findings provide new insights for clinical drug applications to avoid adverse effects.

[Effects of ant nesting on seasonal dynamics of soil CH4 emissions in a tropical rubber-plantation forest]. / 蚂蚁筑巢对热带橡胶人工林土壤甲烷排放季节动态的影响.

Ant nests can affect the process and seasonal dynamics of forest soil methane emissions through mediating methane oxidation/reduction microorganisms and physicochemical environments. To explore the process and mechanism by which ant nests affect soil methane emissions from Hevea brasiliensis plantation in Xishuangbanna, we measured the seasonal dynamics of methane emissions from ant nest and non-nest soils by using static chamber-gas chromatography method, and analyzed the effect of ant nesting on the changes in functional microbial diversity, microhabitats, and soil nutrients in the plantations. The results showed that: 1) Ant nests significantly affected the mean annual soil methane emissions in tropical plantation. Methane emissions in ant nest were decreased by 59.9% than the non-nest soil. In the dry season, ant nest soil was a methane sink (-1.770 µg·m-2·h-1), which decreased by 87.2% compared with the non-nest soil, while it was a methane source (0.703 µg·m-2·h-1) that increased by 152.7% in the wet season. 2) Ant nesting affected methane emissions via changing soil temperature, humidity, carbon and nitrogen concentrations. In contrast to the control, the mean annual temperature, humidity, and carbon and nitrogen content increased by 4.9%-138.5% in ant nest soils, which explained 90.1%, 97.3%, 27.3%-90.0% of the variation in methane emissions, respectively. 3) Ant nesting affected the emission dynamics through changing the diversity and community structure of methane functional microbe. Compared with the control, the average annual methanogen diversity (Ace, Chao1, Shannon, and Simpson indices) in the ant nest ranged from -9.9% to 61.2%, which were higher than those (-8.7%-31.2%) of the methane-oxidising bacterial communities. The relative abundance fluctuations of methanogens and methanotrophic bacteria were 46.76% and -6.33%, respectively. The explaining rate of methanogen diversity to methane emissions (78.4%) was higher than that of oxidizing bacterial diversity (54.5%), the relative abundance explained by the dominant genus of methanogens was 68.9%. 4) The structural equation model showed that methanogen diversity, methanotroph diversity, and soil moisture were the main factors controlling methane emissions, contributing 95.6%, 95.0%, and 91.2% to the variations of emissions, respectively. The contribution (73.1%-87.7%) of soil temperature and carbon and nitrogen components to the emission dynamics was ranked the second. Our results suggest that ant nesting mediates the seasonal dynamics of soil methane emissions, primarily through changing the diversity of methane-function microorganisms and soil water conditions. The research results deepen the understanding of the mechanism of biological regulation of methane emission in tropical forest soil.

Copper-Catalyzed Oxidation of 5-Hydroxymethylfurfural to 2,5-Diformylfuran Assisted by TEMPOL in Liquid Sunlight Methanol.

2,5-Diformylfuran (DFF) is a significant biomass-derived compound with diverse applications in novel furan-based materials, fragrances, fuel additives, and drug synthesis. A pivotal challenge in DFF synthesis is developing a method to produce DFF under mild conditions using sustainable feedstocks. In this study, an affordable 4-hydroxy-2,2,6,6-tetramethylpiperidine (TEMPOL)- assisted Cu(OAc)2 catalytic system for aerobic oxidation reaction of HMF to DFF in liquid sunlight methanol solvent was developed. The effects of parameters such as metal species, catalyst amount, solvent species, ligand structure, and reaction temperature were systematically investigated. The evolution of product distribution in the reaction solution at various times was monitored and analyzed using 1H-NMR spectroscopy. FT-IR and ESI-MS characterizations were employed to integrate experimental findings and elucidate the reaction mechanism. The highest DFF yield of 96% and complete conversion of HMF were obtained. Furthermore, a total DFF yield of 68.6% was achieved from fructose using a two-steps method, demonstrating the potential for scalable production. The establishment of this catalytic system presents a novel approach for the selective preparation of DFF from sustainable feedstocks.

CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation.

AIMS: As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance and malignant progression of gastric cancer (GC). METHODS: In vitro and in vivo models were conducted to investigate the manifestation and impact of CBX4 on cellular senescence and chemoresistance. High-throughput sequencing, chromatin immunoprecipitation, and co-immunoprecipitation techniques were utilized to identify the upstream regulators and downstream effectors associated with CBX4, revealing its intricate regulatory network. RESULTS: CBX4 diminishes the sensitivity of GC cells to cellular senescence, facilitating chemoresistance and GC development by deactivating the senescence-related Hippo pathway. Mechanistically, low-dose cisplatin transcriptionally downregulates CBX4 through CEBPB. In addition, CBX4 preserves the stability and cytoplasm-nuclear transport of YAP1, the key player of Hippo pathway, by inducing SUMO1 modification at K97 and K280, which competitively inhibits YAP1-S127 phosphorylation. CONCLUSIONS: Our study highlights the anti-senescence role of CBX4 and suggests that CBX4 inhibition in combination with low-dose cisplatin has the potential to overcome chemoresistance and effectively restrict GC progression.

Nucleoside Reverse Transcriptase Inhibitors Are the Major Class of HIV Antiretroviral Therapeutics That Induce Neuropathic Pain in Mice.

The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated. In this study, we measured the development of pathological pain and peripheral neuropathy in mice orally treated with distinct antiretrovirals at their translational dosages. Our results show that only nucleoside reverse transcriptase inhibitors (NRTIs), not other types of antiretrovirals such as proteinase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, and CCR5 antagonists, induce pathological pain and PSN. Thus, these findings suggest that NRTIs are the major class of antiretrovirals in cART that promote the development of neuropathic pain. As NRTIs form the essential backbone of multiple different current cART regimens, it is of paramount clinical importance to better understand the underlying mechanism to facilitate the design of less toxic forms of these drugs and/or potential mitigation strategies.

Identification of endothelial protein C receptor as a novel druggable agonistic target for reendothelialization promotion and thrombosis prevention of eluting stent.

The commercially available drug-eluting stent with limus (rapamycin, everolimus, etc.) or paclitaxel inhibits smooth muscle cell (SMC), reducing the in-stent restenosis, whereas damages endothelial cell (EC) and delays stent reendothelialization, increasing the risk of stent thrombosis (ST) and sudden cardiac death. Here we present a new strategy for promoting stent reendothelialization and preventing ST by exploring the application of precise molecular targets with EC specificity. Proteomics was used to investigate the molecular mechanism of EC injury caused by rapamycin. Endothelial protein C receptor (EPCR) was screened out as a crucial EC-specific effector. Limus and paclitaxel repressed the EPCR expression, while overexpression of EPCR protected EC from coating (eluting) drug-induced injury. Furthermore, the ligand activated protein C (APC), polypeptide TR47, and compound parmodulin 2, which activated the target EPCR, promoted EC functions and inhibited platelet or neutrophil adhesion, and enhanced rapamycin stent reendothelialization in the simulated stent environment and in vitro. In vivo, the APC/rapamycin-coating promoted reendothelialization rapidly and prevented ST more effectively than rapamycin-coating alone, in both traditional metal stents and biodegradable stents. Additionally, overexpression or activation of the target EPCR did not affect the cellular behavior of SMC or the inhibitory effect of rapamycin on SMC. In conclusion, EPCR is a promising therapeutical agonistic target for pro-reendothelialization and anti-thrombosis of eluting stent. Activation of EPCR protects against coating drugs-induced EC injury, inflammatory cell, or platelet adhesion onto the stent. The novel application formula for APC/rapamycin-combined eluting promotes stent reendothelialization and prevents ST.

Influence of beeswax-based fish oil oleogels on the mechanism of water and oil retention in Pacific white shrimp (Litopenaeus vannamei) meat emulsion gels: Filling, emulsification and phase transition.

Oleogels have been used in the gelled surimi products to replace animal fats due to its structure characteristics. The effect of structure characteristics in fish oil oleogels on the mechanism of oil/water retention was investigated in meat emulsions. Beeswax assembly improved the oil and water retention. The unsaturation degree of fatty acids lowered the mobility of bound water, immobilized water as well as bound fat in the fish oil oleogel, but enhanced the mobility of free water and protons of unsaturated fatty acids. Beeswax addition and oil phase characteristics could enhance ß-sheets, disulfide bonds and hydrophobic force to improve the viscoelasticity, gel strength and oil/water retention. Beeswax assembly facilitated the tight micro-sol network and filling effect, and high unsaturation degree promoted the emulsification effect, thus reducing phase transition temperature and juice loss. The study could lay the foundation for development of gelled shrimp meat products with EPA and DHA.

Hsa_circ_0004776 regulates the retina neovascularization in progression of diabetic retinopathy via hsa-miR-382-5p/BDNF axis.

The aim of this work was to identify the regulatory function of hsa_circ_0004776 in the progression of diabetic retinopathy (DR). The direct interactions between hsa_circ_0004776 and hsa-miR-382-5p and between hsa-miR-382-5p and BDNF, were confirmed via dual-luciferase reporter assays. Quantitative Real-Time PCR analysis indicated that hsa_circ_0004776 was highly expressed in aqueous humour samples of DR patients and human retinal microvascular epithelial cells (hRECs) under a high-glucose environment, whereas hsa-miR-382-5p showed the opposite trend. Overexpressed hsa_circ_0004776 significantly enhanced DNA synthesis, proliferation, migration, and tube formation in hRECs in hyperglycaemia, while hsa-miR-382-5p mimics reversed these changes. Additionally, in a streptozotocin-induced Sprague-Dawley rat model of DR, vitreous microinjection of rno-miR-382-5p agomir reversed the pathologic features in the progression of DR, including retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis. Our results indicated that under hyperglycaemic conditions, hsa_circ_0004776 influences the progression of DR via hsa-miR-382-5p and thus represents a potential therapeutic target.

Extraction Optimization of Phenolic Compounds from Triadica sebifera Leaves: Identification, Characterization and Antioxidant Activity.

Triadica sebifera (T. sebifera) has attracted much attention because of the high oil content in its seeds, but there are few systematic studies on the phenolic compounds of T. sebifera leaves (TSP). In this study, the extraction process of TSP was optimized by response surface methodology. The phenolic components of these extracts were analyzed by high-performance liquid chromatography (HPLC). Moreover, the effects of hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activity and characterization of T. sebifera leaf extract (TSLE) were evaluated. Under the conditions of ethanol concentration 39.8%, liquid-solid ratio (LSR) 52.1, extraction time 20.2 min and extraction temperature 50.6 °C, the maximum TSP yield was 111.46 mg GAE/g dw. The quantitative analysis and correlation analysis of eight compounds in TSP showed that the type and content of phenolic compounds had significant correlations with antioxidant activity, indicating that tannic acid, isoquercitrin and ellagic acid were the main components of antioxidant activities. In addition, through DPPH and ABTS determination, VD-TSLE and FD-TSLE showed strong scavenging ability, with IC50 values of 138.2 µg/mL and 135.5 µg/mL and 73.5 µg/mL and 74.3 µg/mL, respectively. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) infrared spectroscopy revealed small differences in the extracts of the three drying methods. This study lays a foundation for the effective extraction process and drying methods of phenolic antioxidants from T. sebifera leaves, and is of great significance for the utilization of T. sebifera leaves.

Cost-Effectiveness Analysis of Hepatic Arterial Chemotherapy for Advanced Hepatocellular Carcinoma in China: A Comparative Analysis of HAIC-FO and Sorafenib.

BACKGROUND The FOHAIC-1 trial showed hepatic arterial infusion chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) improved survival, compared with sorafenib, in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to conduct a cost-effectiveness comparison between HAIC-FO and sorafenib from the perspective of the Chinese healthcare system. MATERIAL AND METHODS The economic evaluation was conducted between July 2023 and February 2024, spanning a 10-year investment horizon. A Markov model was developed to perform a cost-effectiveness analysis of HAIC-FO vs sorafenib. Health states incorporated in the model comprised progression-free disease, progressed disease, and death. Transition probabilities were derived from data obtained from the FOHAIC-1 trial. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Additionally, one-way and probabilistic sensitivity analyses assessed the model's robustness. RESULTS The HAIC-FO group accrued a total cost of $22,781, whereas the sorafenib group totaled $18,795. In terms of effectiveness, the HAIC-FO group achieved 1.06 quality-adjusted life years (QALYs), whereas the sorafenib group attained 0.65 QALYs. Compared with sorafenib, HAIC-FO yielded an additional 0.41 QALYs at a cost of additional $3,985, resulting in an incremental cost of $9,720 per QALY gained. The one-way sensitivity analysis revealed the final ICER remained below the willingness-to-pay (WTP) threshold of $30,492 per QALY, when considering parameter fluctuations. Additionally, probabilistic sensitivity analysis indicated a 99.8% probability that the ICER for HAIC-FO compared with sorafenib would fall below the WTP threshold. CONCLUSIONS Compared with sorafenib, HAIC-FO emerged as a cost-effective first-line treatment option for patients facing advanced HCC in China.

Evaluation of traditional Chinese exercise for knee osteoarthritis (KOA): an overview of systematic reviews.

BACKGROUND: Knee osteoarthritis (KOA) has become a public health issue. Several systematic reviews (SRs) and meta-analyses (MAs) indicate that traditional Chinese exercise (TCE) may be an effective treatment for reducing pain and stiffness and improving physical function in people with knee osteoarthritis (KOA). OBJECTIVES: To evaluate the literature quality and evidence for the systematic reviews of TCE for KOA and provide evidence to support the clinical application of TCE for KOA. METHODS: Eight databases were searched from their inception to January 3, 2023, to retrieve relevant literature, including China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Scientific Journal Database (VIP), China Biology Medical literature database (CBM), PubMed, Embase, Web of Science and Cochrane Library, without restrictions on publication date or language. AMSTAR-2 and PRISMA 2020 assessed the methodological and reporting quality of included SRs/MAs. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was utilized to evaluate the quality of evidence. RESULTS: A total of 18 SRs/MAs were included. The methodological quality was "very low" based on AMSTAR-2. The overall reporting quality was deficient based on PRISMA 2020. The quality of Chinese and English literature differed, with English literature being superior in methodological and reporting quality. Among 93 pieces of evidence obtained, 46 (49.46%) were of very low quality, 34 (36.56%) were of low quality, 13 (13.98%) were of moderate quality, and none were of high quality. TCE was supported by 76 pieces of evidence (81.72%). CONCLUSION: TCE appears beneficial and safe for managing KOA. However, due to the relatively low methodological and evidentiary quality of included SRs/MAs, clinicians should interpret these findings cautiously.

A mechanistic analysis of metformin's biphasic effects on lifespan and healthspan in C. elegans: Elixir in youth, poison in elder.

Aging, a complex biological process influenced by genetic, environmental, and pharmacological factors, presents a significant challenge in understanding its underlying mechanisms. In this study, we explored the divergent impacts of metformin treatment on the lifespan and healthspan of young and old C. elegans, demonstrating a intriguing "elixir in youth, poison in elder" phenomenon. By scrutinizing the gene expression changes in response to metformin in young (day 1 of adulthood) and old (days 8) groups, we identified nhr-57 and C46G7.1 as potential modulators of age-specific responses. Notably, nhr-57 and C46G7.1 exhibit contrasting regulation patterns, being up-regulated in young worms but down-regulated in old counterparts following metformin treatment. Functional studies employing knockdown approaches targeting nhr-57, a gene under the control of hif-1 with a documented protective function against pore-forming toxins in C. elegans, and C46G7.1, unveiled their critical roles in modulating lifespan and healthspan, as well as in mediating the biphasic effects of metformin. Furthermore, deletion of hif-1 retarded the influence of metformin, implicating the involvement of hif-1/nhr-57 in age-specific drug responses. These findings underscored the necessity of deciphering the mechanisms governing age-related susceptibility to pharmacological agents to tailor interventions for promoting successful aging.

Dynamic evolution of MADS-box genes in extant ferns via large-scale phylogenomic analysis.

Introduction: Several studies of MADS-box transcription factors in flowering plants have been conducted, and these studies have indicated that they have conserved functions in floral organ development; MIKC-type MADS-box genes has been proved to be expanded in ferns, however, few systematic studies of these transcription factors have been conducted in non-seed plants. Although ferns and seed plants are sister groups, they exhibit substantial morphological differences. Methods: Here, we clarified the evolution of MADS-box genes across 71 extant fern species using available transcriptome, genome, and gene expression data. Results: We obtained a total of 2,512 MADS-box sequences, ranging from 9 to 89 per species. The most recent common ancestor (MRCA) of ferns contained approximately three type I genes and at least 5-6 type II MADS-box genes. The domains, motifs, expression of type I and type II proteins, and the structure of the both type genes were conserved in ferns as to other land plants. Within type II genes, MIKC*-type proteins are involved in gametophyte development in ferns; MIKCC-type proteins have broader expression patterns in ferns than in seed plants, and these protein sequences are likely conserved in extant seed plants and ferns because of their diverse roles in diploid sporophyte development. More than 90% of MADS-box genes are type II genes, and MIKCC genes, especially CRM1 and CRM6-like genes, have undergone a large expansion in leptosporangiate ferns; the diverse expression patterns of these genes might be related to the fuctional diversification and increased complexity of the plant body plan. Tandem duplication of CRM1 and CRM6-like genes has contributed to the expansion of MIKCC genes. Conclusion or Discussion: This study provides new insights into the diversity, evolution, and functions of MADS-box genes in extant ferns.

One Pot Synthesis of New Benzimidazole Derivatives with Exceptionally High Luminescence Quantum Efficiency.

AIM AND OBJECTIVES: There are different approaches to the synthesis of benzimidazole. In this article, five new benzimidazole derivatives, BMPO, Me-BMPO, Di-MeBMPO, F-BMPO and Cl-BMPO where (BMPO=3-[(1H)-benzo[d]imidazol-2-yl]pyridin-2(1H)-one), have been prepared. Another study was carried out on luminescence properties and their potential applications for the detection of transition metal ions. MATERIALS AND METHODS: From the one-pot synthesis approach, all the derivatives of the benzimidazole compounds were obtained. The compounds were characterized using HRMS, 1HNMR, 13CNMR, and X-ray crystallography. Herein, a mechanism has been deciphered by predicting the release of HCl(g). RESULTS: All compounds showed a strong deep blue emission when dissolved in dimethylacetamide (DMA), with emission wavelengths at 423, 428, 435, 423, and 421 nm, and half-times of 3.64, 2.77, 2, 19, 3.42 and 3.52 ns, respectively. In addition, their emission quantum yields were determined to be 72, 50, 42, 73 and 80%. CONCLUSION: Five new benzimidazole derivatives, BMPO, Me-BMPO, Di-MeBIPO, F-BIPO, and Cl-BIPO, have been successfully synthesized by the one-pot synthesis method, and their structures are characterized and confirmed. The compounds exhibited exceptional luminescence by emitting a strong blue light in DMA with high fluorescence quantum yields between 42~80%.