Search

Abstract Background This study aimed to evaluate the efficacy and safety of thermal ablation in the treatment of patients with Bethesda IV thyroid nodules (follicular neoplasms) by analyzing large-scale data on various outcomes. Materials and methods Literature searches were conducted in PUBMED, EMBASE, Web of Science, and the Cochrane Library for studies on the use of thermal ablation in patients with Bethesda IV thyroid nodules published from March 1, 2014, to March 1, 2024. Data on volume change at 12 months; the volume reduction rate (VRR) at 1, 3, 6, and 12 months; the complete disappearance rate (CDR); and the complication rate were evaluated. All the data were analyzed with STATA 15. Results Five eligible studies were included. The findings indicate that thermal ablation is both effective and safe. The mean change in tumor volume at 12 months postthermal ablation was characterized by a standardized mean difference (SMD) of -1.13 (95% CI: -1.36 - -0.90, p = 0.000). Specifically, the mean changes in tumor volume at 12 months after radiofrequency ablation (RFA) and microwave ablation (MWA) were − 1.19 (95% CI: -1.75 - -0.64) and − 1.26 (95% CI: -1.71 - -0.81), respectively. The VRRs at 1, 3, 6, and 12 months postthermal ablation were 43% (95% CI: 33 − 53%), 47% (95% CI: 20 − 74%), 69% (95% CI: 62 − 76%), and 85% (95% CI: 79 − 90%), respectively. The VRRs at 12 months after RFA and MWA were 84% (95% CI: 76 − 91%) and 85% (95% CI: 75 − 95%), respectively. The VRR at 12 months, stratified by initial nodule size, was 84% (95% CI: 77 − 91%) and 86% (95% CI: 78 − 94%). The CDR at the final follow-up was 88% (95% CI: 80 − 95%). The complication rate was 4.0% (95% CI: 0.0 − 8.0%), with pain and hoarseness being the most frequently reported complications; no life-threatening complications were documented. Conclusions Thermal ablation is a reliable treatment for Bethesda IV thyroid nodules, and RFA and MWA are advantageous treatment strategies. However, more prospective, multicenter, and large-sample studies are needed in the future.

China has committed to achieving carbon neutrality by 2060. It is essential to develop representative CO2 emissions pathways at the provincial level that align with the national target to facilitate effective policy implementation and scientific research. To address inconsistencies between provincial aggregate emissions and national estimates, this study compares the 2021 CO2 emissions estimates of China's provinces from the bottom‒up emissions factor method and the top‒down atmospheric CO2 concentration inversion method. We find that these methods yield comparable results for the emissions from energy combustion and industrial processes at the provincial level. Based on a review of existing research on CO2 pathways for China's provinces, we propose a set of representative pathways for China's provinces. These pathways align with past practices of allocating national emissions intensity reduction targets to provinces and are consistent with the national Tsinghua‒CMA pathway. The proposed pathways require provinces to sequentially peak their emissions by 2030, followed by rapid emissions reduction. Compared to a reference scenario without the carbon neutrality target, these pathways would incur an estimated cumulative GDP loss of about 1% between 2020 and 2060. However, there are notable regional variations, with some regions in the northwest potentially experiencing higher economic growth due to the availability of high-quality low-carbon resources. We recommend that China enhance provincial-level CO2 emissions accounting by cross-validating bottom‒up and top‒down methods. Additionally, careful consideration should be given to aligning provincial targets with national and global commitments when updating pathways toward carbon neutrality.

Abstract This study investigated the impact of LNP023 on the AMPK/mTOR signaling pathway in lupus nephritis (LN) and its effects on autophagy and oxidative stress. A mouse model of LN was established, and renal injury was confirmed by assessing various LN markers, including antinuclear antibody, ds‐DNA, anti‐Sm antibody, and others. Mice were treated with LNP023, the AMPK activator AICAR, or the AMPK inhibitor dorsomorphin. Renal injury and fibrosis were evaluated using HE and Masson staining. Expression levels of AMPK, mTOR, LC3, Beclin1, and p62 were assessed by immunohistochemistry and Western blot. Oxidative stress and inflammatory markers were measured by polymerase chain reaction and enzyme‐linked immunosorbent assay. LN mice exhibited low AMPK/p‐AMPK and high mTOR/p‐mTOR levels, alongside significant renal injury, fibrosis, reduced autophagy, and elevated oxidative stress. LNP023 treatment improved these parameters, with enhanced effects when combined with AICAR. Conversely, dorsomorphin reversed LNP023's therapeutic benefits. The complement factor B inhibitor LNP023 promotes kidney health in LN mice by mediating the AMPK/mTOR pathway, promoting autophagy, and attenuating oxidative stress.

Hydrogen and electricity are crucial and interdependent energy carriers in China's pursuit of carbon neutrality, suggesting the necessity of utilizing cost-effective low-carbon technologies that facilitate their integrated development. The cost-optimal, provincial level, deployment of low-carbon technologies under this long-term goal remains to be determined. This study employs the REPO model to identify the cost-optimal, low-carbon hydrogen production mixes and the evolution of the integrated power system of China from 2020 to 2050. The integrated planning and operation of hydrogen supply and power systems are explored at the provincial level. The role of high-temperature gas-cooled reactors in this integrated energy system is also analyzed. The results reveal that electrolytic hydrogen would dominate China's hydrogen supply after 2040, with alkaline, proton exchange membrane, and solid oxide electrolyzers produce over 1 Mt of hydrogen in the short term, by 2035, and in 2050. Leveraging the low-carbon heat production of high-temperature gas-cooled reactors in addition to its electricity generation to meet the thermal requirements of solid oxide electrolyzers could boost the output to 4.2 Mt in 2050 and reducing the total system CO2 emissions and costs by 2.28% and 0.05%, respectively. By 2050, the integration of hydrogen supply and power systems also generates up to 2194 TW h of flexible electricity demand by electrolyzers, which raised the renewable energy penetration by 4 percentage points while decreasing the need of flexible natural gas power generations and energy storages. This study is valuable for proposing the analytical framework and performing the provincial-level study of decarbonization of China's integrated hydrogen supply and power system.

Abstract Background Stress-induced activation of ERK/Drp1 serves as a checkpoint in the segregation of damaged mitochondria for autophagic clearance (mitophagy). Elevated cytosolic calcium (Ca2+) activates ERK, which is pivotal to mitophagy initiation. This process is altered in Parkinson’s disease (PD) with mutations in leucine-rich repeat kinase 2 (LRRK2), potentially contributing to mitochondrial dysfunction. Pathogenic LRRK2 mutation is linked to dysregulated cellular Ca2+ signaling but the mechanism involved remains unclear. Methods Mitochondrial damages lead to membrane depolarization. To investigate how LRRK2 mutation impairs cellular response to mitochondrial damages, mitochondrial depolarization was induced by artificial uncoupler (FCCP) in wild-type (WT) and LRRK2R1441G mutant knockin (KI) mouse embryonic fibroblasts (MEFs). The resultant cytosolic Ca2+ flux was assessed using live-cell Ca2+ imaging. The role of mitochondria in FCCP-induced cytosolic Ca2+ surge was confirmed by co-treatment with the mitochondrial sodium-calcium exchanger (NCLX) inhibitor. Cellular mitochondrial quality and function were evaluated by Seahorse™ real-time cell metabolic analysis, flow cytometry, and confocal imaging. Mitochondrial morphology was visualized using transmission electron microscopy (TEM). Activation (phosphorylation) of stress response pathways were assessed by immunoblotting. Results Acute mitochondrial depolarization induced by FCCP resulted in an immediate cytosolic Ca2+ surge in WT MEFs, mediated predominantly via mitochondrial NCLX. However, such cytosolic Ca2+ response was abolished in LRRK2 KI MEFs. This loss of response in KI was associated with impaired activation of Ca2+/calmodulin-dependent kinase II (CaMKII) and MEK, the two upstream kinases of ERK. Treatment of LRRK2 inhibitor did not rescue this phenotype indicating that it was not caused by mutant LRRK2 kinase hyperactivity. KI MEFs exhibited swollen mitochondria with distorted cristae, depolarized mitochondrial membrane potential, and reduced mitochondrial Ca2+ store and mitochondrial calcium uniporter (MCU) expression. These mutant cells also exhibited lower cellular ATP: ADP ratio albeit higher basal respiration than WT, indicating compensation for mitochondrial dysfunction. These defects may hinder cellular stress response and signals to Drp1-mediated mitophagy, as evident by impaired mitochondrial clearance in the mutant. Conclusions Pathogenic LRRK2R1441G mutation abolished mitochondrial depolarization-induced Ca2+ response and impaired the basal mitochondrial clearance. Inherent defects from LRRK2 mutation have weakened the cellular ability to scavenge damaged mitochondria, which may further aggravate mitochondrial dysfunction and neurodegeneration in PD.

Soil tensile strength is a critical parameter governing the initiation and propagation of tensile cracking. This study proposes an eco-friendly approach to improve the tensile behavior and crack resistance of clayey soils. To validate the feasibility and efficacy of the proposed approach, direct tensile tests were employed to determine the tensile strength of the compacted soil with different W-OH treatment concentrations and water contents. Desiccation tests were also performed to evaluate the effectiveness of W-OH treatment in enhancing soil tensile cracking resistance. During this period, the effects of W-OH treatment concentration and water content on tensile properties, soil suction and microstructure were investigated. The tensile tests reveal that W-OH treatment has a significant impact on the tensile strength and failure mode of the soil, which not only effectively enhances the tensile strength and failure displacement, but also changes the brittle failure behavior into a more ductile quasi-brittle failure behavior. The suction measurements and mercury intrusion porosimetry (MIP) tests show that W-OH treatment can slightly reduce soil suction by affecting skeleton structure and increasing macropores. Combined with the microstructural analysis, it becomes evident that the significant improvement in soil tensile behavior through W-OH treatment is mainly attributed to the W-OH gel's ability to provide additional binding force for bridging and encapsulating the soil particles. Moreover, desiccation tests demonstrate that W-OH treatment can significantly reduce or even inhibit the formation of soil tensile cracking. With the increase of W-OH treatment concentration, the surface crack ratio and total crack length are significantly reduced. This study enhances a fundamental understanding of eco-polymer impacts on soil mechanical properties and provides valuable insight into their potential application for improving soil crack resistance.

Abstract Background In patients undergoing breast-conserving therapy without surgical clip implantation, the accuracy of tumor bed identification and the consistency of clinical target volume (CTV) delineation under computed tomography (CT) simulation remain suboptimal. This study aimed to investigate the feasibility of implementing preoperative magnetic resonance (MR) simulation on delineations by assessing interobserver variability (IOV). Methods Preoperative MR and postoperative CT simulations were performed in patients who underwent breast-conserving surgery with no surgical clips implanted. Custom immobilization pads were used to ensure the same supine position. Three radiation oncologists independently delineated the CTV of tumor bed on the images acquired from MR and CT simulation registration and CT simulation alone. Cavity visualization score (CVS) was assigned to each patient based on the clarity of the tumor bed on CT simulation images. IOV was indicated by generalized conformity index (CIgen), denoted as CIgen−CT and CIgen−MR/CT, and the distance between the centroid of mass (dCOM), denoted as dCOMCT and dCOMMR/CT. The variation of IOV in different CVS subgroups was analyzed. Results A total of 10 patients were enrolled in this study. The median and interquartile range (IQR) of maximum pathological diameter of the tumors in all patients were 1.55 (0.80–1.92) cm. No statistical significance was found between the volumes of CTVs on CT simulation and on MR/CT simulation registration images (p = 0.387). CIgen−MR/CT was significantly larger than CIgen−CT (p = 0.005). dCOMMR/CT was significantly smaller than dCOMCT (p = 0.037). The median and IQR of CVS in all patients were 2.34 (2.00–3.08). The difference of CIgen between CIgen−MR/CT and CIgen−CT was larger in the low CVS group (p = 0.016). The difference of dCOM showed a decreasing trend when CVS was lower, although it did not reach statistical significance (p = 0.095). Conclusions For patients who underwent breast-conserving surgery without surgical clip implantation, the use of preoperative MR simulation in delineating the CTV of tumor bed decreased the IOV among observers. The consistency of tumor bed identification was improved especially in cases where the margins of tumor bed were challenging to visualize on CT simulation images. The study findings offer potential benefits in reducing local recurrence and minimizing tissue irritation in the surrounding areas. Future investigation in a larger patient cohort to validate our results is warranted.

BackgroundBranched-chain amino acids (BCAAs) are widely used as sports nutrition supplements. However, their impact on the rate of force development (RFD), an indicator of explosive muscle strength, has not yet been validated. This study aimed to assess the impact of BCAA supplementation on the RFD in college basketball players during simulated games.MethodsThis study employed a randomized, controlled crossover, double-blind design. Participants received either BCAAs (0.17 g/kg combined with 0.17 g/kg isocaloric glucose) or a placebo (0.34 g/kg isocaloric glucose) orally 30 min before beginning the exercise protocol. The RFD was quantified using the isometric mid-thigh pull (IMTP) test. Additional outcome measures, including strength and jump tests, agility and sprinting tests, and physiological responses, were also assessed. A two-way repeated measures ANOVA was employed to evaluate the impact of supplements (BCAAs and placebo) on RFD and other related outcome measures.ResultsAnalysis of the 50 ms RFD demonstrated significant main effects of BCAA supplementation (p = 0.003). The BCAAs group consistently exhibited higher levels of 50 ms RFD compared to the placebo group across rounds 1 to 4. For example, in round 1, the 50 ms RFD was 3702.3 ± 1223.2 N/S in the BCAAs group versus 2931.3 ± 888.8 N/S in the placebo group (p = 0.045). Although no significant between-group differences were observed for the 100, 150, 200, and 250 ms RFD measurements, the BCAAs group consistently showed superior values across all time points. The results of other outcome indicators also suggested that supplementation with BCAAs was indeed effective.ConclusionThe results indicate that BCAA supplementation can enhance RFD in basketball players, particularly at the 50 ms RFD. Our research design provides reliable insights into the effects of BCAAs on athletic performance. Further studies of similar design with larger sample sizes are necessary to confirm and extend these findings.Clinical trial registrationChinese Clinical Trial Registry, ChiCTR2400091314 (https://www.chictr.org.cn).

Soil cracking induced by extreme drought represents a widespread natural phenomenon occurring across the earth surface, capable of triggering multiple weakening mechanisms within surface soils, potentially leading to the instability and failure of slopes and agricultural infrastructures. This study proposes an innovative geophysical monitoring framework for detecting field soil cracking by combining the actively heated fiber-optic (AHFO) method and distributed fibre optical sensing (DFOS) based on optical frequency domain reflectometry (OFDR) technique, referred to as AH-OFDR framework. Laboratory calibration tests, field monitoring tests, numerical simulations, and sensitivity analyses were employed to comprehensively evaluate the feasibility, effectiveness, and limitations of the AH-OFDR framework for soil crack monitoring. Laboratory calibration confirmed that the DFOS-OFDR technique achieves a minimum spatial resolution and readout accuracy of 1 mm, along with a temperature measurement accuracy of ±0.1 °C. Field monitoring verified that the AH-OFDR framework can accurately detect soil cracks ranging in width from 0.01 m to 0.12 m. Additionally, numerical simulations not only validated the effectiveness of the AH-OFDR framework across a broader range of crack widths, from 0.01 m to 0.50 m, but also established a quantitative relationship between temperature changes and the spatial distribution of crack positions and widths. Notably, a critical crack width threshold of 0.30 m was identified within the AH-OFDR framework, significantly impacting the prediction of soil crack widths. Sensitivity analysis demonstrated the remarkable crack detection capabilities of the AH-OFDR framework, irrespective of the soil crack width and spacing. The AH-OFDR framework holds substantial potential as an innovative and high-resolution observational method for advancing our understanding of diverse geological and hydrogeological processes.

Abstract Background Atrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by β-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of β-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues . Methods We compared the difference of β-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of β-catenin in the development of AF was also explored in mice and primary cells. Results Firstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of β-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, β-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3β (GSK-3β) and Adenomatous Polyposis Coli (APC), which participated in the degradation of β-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting β-catenin expression in the AF model mice. Conclusions Based on human atrial pathological and molecular analyses, our findings provided evidence that β-catenin was associated with atrial fibrosis and AF progression.

Introduction: Lipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance. Methods: Untargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes. Results: Long-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage. Conclusion: LCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS.

BackgroundFatigue and muscular fitness are closely related to the quality of life in patients with multiple sclerosis (MS). However, the optimal exercise dosage to improve these outcomes remains unclear.ObjectiveWe evaluated the effects of different exercise modalities and dosages on fatigue levels and muscular fitness in patients with MS.MethodsA systematic search was conducted across five electronic databases, including randomized controlled trials involving exercise interventions for patients with MS. The data covered literature from the establishment of each database up to August 2024. Two independent reviewers assessed the quality of the studies. Network and dose–response meta-analyses were performed using a random-effects model to evaluate the impact of exercise.ResultsA total of 84 papers were included, involving 3,786 participants. The network meta-analysis revealed that mind–body exercise (MBE) had the most significant effect on reducing fatigue (SMD = −0.94; 95% CrI: −1.3 to −0.6), followed by resistance training (RT) (SMD = −0.86; 95% CrI: −1.2 to −0.58), combined exercise (COM) (SMD = −0.70; 95% CrI: −1.2 to −0.22), and high-intensity interval training (HIIT) (SMD = −0.50; 95% CrI: −1.1 to 0.14). Additionally, HIIT were found to be the most effective in improving muscular fitness (SMD = −0.86; 95% CrI: −1.5 to −0.27), followed by COM (SMD = −0.81; 95% CrI: −1.2 to −0.41), MBE (SMD = −0.64; 95% CrI: −1.1 to −0.16), and RT (SMD = −0.62; 95% CrI: −0.89 to −0.16). Moreover, a dose as low as 240 METs-min/week was sufficient to improve fatigue, while a dose of 430 METs-min/week was required to enhance muscular fitness. The optimal dose for reducing fatigue was 650 METs-min/week, and the best dose for improving muscular fitness was 530 METs-min/week.ConclusionExercise is an effective method for improving fatigue and muscular fitness in patients with MS. While MBE and COM rank relatively higher compared to other exercise modalities. The optimal exercise dosage for reducing fatigue and improving muscular fitness ranges between approximately 530 to 860 MET-minutes per week.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42024577643.

Summary: Fate determination of neural stem cells (NSCs) is crucial for cortex development and is closely linked to neurodevelopmental disorders when gene expression networks are disrupted. The transcriptional corepressor chromodomain Y-like (CDYL) is widely expressed across diverse cell populations within the human embryonic cortex. However, its precise role in cortical development remains unclear. Here, we show that CDYL is critical for human cortical neurogenesis and that its deficiency leads to a substantial increase in gamma-aminobutyric acid (GABA)-ergic neurons in cortical organoids. Subsequently, neuronatin (NNAT) is identified as a significant target of CDYL, and its abnormal expression obviously influences the fate commitment of cortical NSCs. Cross-species comparisons of CDYL targets unravel a distinct developmental trajectory between human cortical organoids and the mouse cortex at an analogous stage. Collectively, our data provide insight into the evolutionary roles of CDYL in human cortex development, emphasizing its critical function in maintaining the fate of human cortical NSCs.

Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16 S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.

Diabetic nephropathy (DN) is one of the most common chronic complications in patients with diabetes and remains a leading cause of end-stage renal disease. Despite current treatment strategies focusing primarily on blood glucose control and antihypertensive medications, their efficacy is often limited, failing to halt disease progression effectively. However, Shen-Shuai-Ning (SSN), a traditional Chinese medicine compound, has demonstrated significant clinical efficacy in DN treatment in recent years. SSN exerts multifaceted effects, including immunomodulation, attenuation of oxidative stress, and inhibition of fibrosis, leading to improvements in renal function indices and reductions in proteinuria levels, with favorable tolerability. Furthermore, when combined with conventional treatments, SSN exhibits enhanced therapeutic efficacy, providing a comprehensive and effective treatment strategy for DN patients. Future research endeavors should prioritize large-scale, multicenter clinical trials to validate its efficacy and safety across diverse populations, thereby further advancing its integration into clinical practice.

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown. Design: Retrospective cohort study. Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations. Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the role of HOXA transcript at the distal tip (HOTTIP) in its pathogenesis remains underexplored. This study investigates the mechanism by which HOTTIP influences apoptosis and the inflammatory response of fibroblast‐like synoviocytes (FLS). An RA mouse model was established, and clinical scores were analyzed. Pathological changes in synovial tissues, bone mineral density (BMD) of the paws, serum tartrate‐resistant acid phosphatase (TRAP) activity, and TNF‐α and IL‐1β levels were assessed. FLS were transfected, and cell proliferation and apoptosis were examined. The RNA‐pull‐down assay determined HOTTIP's interaction with mixed‐lineage leukemia 1 (MLL1), while RNA immunoprecipitation assay measured HOTTIP expression pulled down by MLL1. The levels of MLL1 and toll‐like receptor 4 (TLR4) after MLL1 overexpression based on HOTTIP silencing were determined. Chromatin immunoprecipitation (ChIP) was performed with H3K4me3 as an antibody, followed by the evaluation of TLR4 expression. HOTTIP expression was elevated in RA mouse synovial tissues. Inhibition of HOTTIP led to reduced clinical scores, inflammatory infiltration, synovial hyperplasia, TRAP activity, and TNF‐α and IL‐1β levels, along with increased BMD. In vitro Interference with HOTTIP suppressed RA‐FLS apoptosis and inflammation. HOTTIP upregulated TLR4 expression by recruiting MLL1 to facilitate TLR4 promoter methylation. MLL1 overexpression reversed HOTTIP silencing‐mediated repression of RA‐FLS apoptosis. Activation of H3K4 methylation counteracted HOTTIP knockout, ameliorating the inflammatory response. HOTTIP regulates TLR4 expression by recruiting MLL1, leading to TLR4 promoter methylation, thereby suppressing RA‐FLS proliferation and inducing cell apoptosis and inflammatory response in RA.

Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

Detect the expression of Farnesoid X Receptor(FXR), Multiple Drug Resistance Associated Protein-1(MRP-1) and Solute Carrier Family 7, Member 5 (SLC7A5) in hepatocellular carcinoma(HCC) of rat model, so as to provide new therapeutic targets for gene therapy of HCC. Sixty male Wistar rats were randomly divided into three groups. The rats in experimental group were given 0.2% diethylnitrosamine (DEN) by gavage with a dose of 10 mg/kg, 3 times a week, and it stopped at 12 weeks. The control group rats were given physiological saline by gavage, while the sham operation group did not receive anything by gavage. At 10 weeks, one rat in the experimental group was euthanized, and the changes of livers were recorded. The procedure was repeated at 12 weeks. After 12 weeks, HCC only occurred in the experimental group. After confirming the formation of the tumor through pathological examination, liver tissues and tumor tissues were taken from the three groups. FXR, MRP-1 and SLC7A5 expression in liver tissues and tumor tissues was detected. After 7 weeks the rats in experimental group ate less, and their weight was significantly reduced. Three months later, HCC was detected in 15 rats in the experimental group. The ratio of FXR/GAPDH mRNA, MRP-1/GAPDH mRNA, SLC7A5/GAPDH mRNA were significantly different among the three groups. Under the light microscope the FXR protein, MRP-1 protein, and SLC7A5 protein react with their respective antibodies, and they showed granular expression. Every pathological section included different numbers of positive cells in each group. FXR expression in HCC of rats was significantly lower than that in normal liver tissues, but MRP-1 and SLC7A5 expression in HCC were significantly higher than that in normal liver tissues, suggesting that drugs targeting FXR, MRP-1 and SLC7A5 may be new strategies for the treatment of HCC.

ABSTRACT Introduction Lung adenocarcinoma (LUAD) is one of the major histopathological types of non‐small cell lung cancer (NSCLC), including solid, acinar, lepidic, papillary and micropapillary subtypes. Increasing evidence has shown that micropapillary LUAD is positively associated with a higher percentage of driver gene mutations, a higher incidence of metastasis and a poorer prognosis, while lepidic LUAD has a relatively better prognosis. However, the novel genetic change and its underlying mechanism in the progression of micropapillary LUAD have not been exactly determined. Methods A total of 181 patients with LUAD who underwent surgery at the First Affiliated Hospital of Huzhou University from January 2020 to December 2022 were enrolled. Three predominant lepidic and three predominant micropapillary LUAD tissue samples were carried out using whole‐exome sequencing. Comprehensive analysis of genomic variations and the difference between lepidic and micropapillary LUAD was performed. In addition, the TMEM229A Q200del mutation was verified using our cohort and TCGA‐LUAD datasets. The correlations between the TMEM229A Q200del mutation and the clinicopathological characteristics of patients with LUAD were further analyzed. The functions and mechanisms of TMEM229A Q200del on NSCLC cell proliferation and migration were also determined. Results The frequency of genomic changes in patients with micropapillary LUAD was higher than that in patients with lepidic LUAD. Mutations in EGFR, ATXN2, C14orf180, MUC12, NOTCH1, and PKD1L2 were concomitantly detected in three predominant micropapillary and three predominant lepidic LUAD cases. The TMEM229A Q200del mutation was only mutated in lepidic LUAD. Additionally, the TMEM229A Q200del mutation had occurred in 16 (8.8%) patients, and not found TMEM229A R76H and M346T mutations in our cohort, while TMEM229A mutations (R76H, M346T, and Q200del) occurred only in 1.0% of the TCGA‐LUAD cohort. Further correlation analysis between the TMEM229A Q200del mutation and clinicopathological characteristics suggested that a lower frequency of the Q200del mutation was significantly associated with positive lymph node metastasis, advanced TNM stage, positive cancer thrombus, and pathological features. Finally, overexpression of TMEM229A Q200del suppressed NSCLC cell proliferation and migration in vitro. Mechanistically, overexpression of TMEM229A and TMEM229A Q200del both reduced the expression level of phosphorylated (p)‐ERK and p‐AKT (Ser473), and the reduced protein level of p‐ERK in the TMEM229A Q200del group was more pronounced compared to the TMEM229A group. Conclusion Our results demonstrated that the TMEM229A Q200del mutant may play a protective role in the progression of LUAD via inactivating ERK pathway, providing a potential therapeutic target in LUAD.

BackgroundThere is a link between cardiovascular diseases and intestinal permeability, but it is not clear. This review aimed to elucidate intestinal permeability in cardiovascular diseases by meta-analysis.MethodsMultidisciplinary electronic databases were searched from the database creation to April 2023. All included studies were assessed for risk of bias according to the Joanna Briggs Institute Critical Appraisal Checklist. The heterogeneity of each study was estimated using the I2 statistic, and the data were analyzed using Review Manager 5.3 and Stata 16.0.ResultsIn total, studies in 13 pieces of literature were included in the quantitative meta-analysis. These studies were conducted among 1,321 subjects mostly older than 48. Patients had higher levels of intestinal permeability markers (lipopolysaccharide, d-lactate, zonulin, serum diamine oxidase, lipopolysaccharide-binding protein, intestinal fatty acid binding protein, and melibiose/rhamnose) than controls (standard mean difference SMD = 1.50; 95% CI = 1.31–1.88; p

Civil engineering structures under ambient excitations are essentially time-varying and nonlinear structural systems and the resultant response signals exhibit non-stationarity. To reveal the time-varying characteristics of non-stationary signals, time frequency analysis methods with high resolutions are required. Although synchroextracting short time Fourier transform (SESTFT) is able to generate more energy concentrated time frequency representations and allow signal reconstruction, its major disadvantage is the window function is fixed. To address this issue, an enhanced synchroextracting wavelet transform (ESEWT) method is proposed to refine frequency bands by combing synchroextracting and continuous wavelet transform. After that, dynamic optimization (DO) is used to extract instantaneous frequency (IF) curves within the refined frequency bands. Two numerical examples and an experimental study case are investigated to illustrate the effectiveness and accuracy of the proposed method. The results demonstrate that the proposed ESEWT is capable of extracting frequency bands more accurately and its combination with DO identifies IFs of non-stationary signals better than current time frequency analysis methods such as SESTFT.

Abstract Background Corpus callosum glioblastoma (ccGBM) is a specific type of GBM and has worse outcomes than other non-ccGBMs. We sought to identify whether en-bloc resection of ccGBMs based on T2-FLAIR imaging contributes to clinical outcomes and can achieve a satisfactory balance between maximal resection and preservation of neurological function. Methods A total of 106 adult ccGBM patients (including astrocytoma, WHO grade 4, IDH mutation, and glioblastoma) were obtained from the Department of Neurosurgery in Nanfang Hospital between January 2008 and December 2018. The clinical data, including gender, age, symptoms, location of tumor, involvement of eloquent areas, extent of resection (EOR), pre- and postoperative Karnofsky Performance Status (KPS) scales, and National Institute of Health stroke scale (NIHSS) scores were collected. Propensity score matching (PSM) analysis was applied to control the confounders for analyzing the relationship between the en-bloc technique and EOR, and the change in the postoperative KPS scales and NIHSS scores. Results Applying the en-bloc technique did not negatively affect the postoperative KPS scales compared to no-en-bloc resection (P = 0.851 for PSM analysis) but had a positive effect on preserving or improving the postoperative NIHSS scores (P = 0.004 for PSM analysis). A positive correlation between EOR and the en-bloc technique was identified (r = 0.483, P

Abstract Objective The aim of this study was to evaluate the outcome and risk factors for chairside CAD/CAM full cusp coverage restorations on endodontically treated posterior teeth after 3 years of follow-up. Methods A total of 245 endodontically treated posterior teeth of 224 patients were included and restored with CAD/CAM full cusp coverage all-ceramic restorations according to a standardized protocol. Patients were recalled after treatments 1 to 3 years and underwent clinical and radiological examinations. At recall, modified FDI criteria were used to determine treatment outcomes by 2 evaluators. Success was determined when FDI scores were 1–2, and failure was indicated when FDI scores were 5. Logistic regression analysis was performed to evaluate potential risk factors. Results A total of 183 patients presented at recall, and the clinical outcomes of 201 teeth were analyzed with a recall rate of 82.0% for teeth and 81.7% for patients after 1–3 years of follow-up.185 of 201 teeth were found to have FDI scores of 1–2, and the success rate was 92%. No teeth were extracted during the follow-up period. Fourteen failed cases with an FDI score of 5 presented restoration dislocation, fracture of restoration or/and tooth. Logistic regression analysis revealed that oral parafunction (OR 2.281, 95% CI 2.2 ~ 47.5, P value 0.01) was a risk factor for success rate. Conclusion Chairside CAD/CAM all-ceramic full cusp coverage restoration was (could be) a promising alternative for restoring endodontically treated posterior teeth.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Abstract The concept of Terahertz Field-Induced Second Harmonic (TFISH) Generation is revisited to introduce a single-shot detection scheme based on third order nonlinearities. Focused specifically on the further development of THz plasma-based sources, we begin our research by reimagining the TFISH system to serve as a direct plasma diagnostic. In this work, an optical probe beam is used to mix directly with the strong ponderomotive current associated with laser-induced ionization. A four-wave mixing (FWM) process then generates a strong second-harmonic optical wave because of the mixing of the probe beam with the nonlinear current components oscillating at THz frequencies. The observed conversion efficiency is high enough that for the first time, the TFISH signal appears visible to the human eye. We perform spectral, spatial, and temporal analysis on the detected second-harmonic frequency and show its direct relationship to the nonlinear current. Further, a method to detect incoherent and coherent THz inside plasma filaments is devised using spatio-temporal couplings. The single-shot detection configurations are theoretically described using a combination of expanded FWM models with Kostenbauder and Gaussian Q-matrices. We show that the retrieved temporal traces for THz radiation from single- and two-color laser-induced air-plasma sources match theoretical descriptions very well. High temporal resolution is shown with a detection bandwidth limited only by the spatial extent of the probe laser beam. Large detection bandwidth and temporal characterization is shown for THz radiation confined to under-dense plasma filaments induced by

AbstractInflammatory markers have a wide range of predictive values in the prognosis of non-small lung cancer (NSCLC). Poor nutritional status usually means a poor prognosis in patients with NSCLC, which is widely recognized by oncologists and nutritionists. Serum albumin has a certain value in evaluating the prognosis of patients. Several inflammatory albumin-related markers have been proposed, but they have not been widely used in predicting the prognosis of NSCLC in clinical practice. We aim to systematically review the published clinical evidence of albumin-related inflammatory markers in predicting the prognosis of NSCLC and to describe their progress and value. The results showed that the markers included in the review could be prognostic indicators in patients with NSCLC. However, we found that the cut-off value of albumin-related inflammatory markers with quantitative nature was very chaotic and needed to be defined by recognized standards. We summarized and compared the advantages and disadvantages of these markers, but a prospective cohort study with long-term follow-up after adjustment for important confounders is still necessary. Whether the results and conclusions could be directly applied in clinical practice needs to be identified and evaluated. There is an urgent need to classify and standardize the albumin-related inflammatory markers that play an important role in the prognosis of NSCLC, which is the key to ensuring the transformation from clinical study to clinical application.

Bibenzyl compounds are one of the most important bioactive components of natural medicine. However, Dendrobium officinale as a traditional herbal medicine is rich in bibenzyl compounds and performs functions such as acting as an antioxidant, inhibiting cancer cell growth, and assisting in neuro-protection. The biosynthesis of bibenzyl products is regulated by bibenzyl synthase (BBS). In this study, we have cloned the cDNA gene of the bibenzyl synthase (DoBS1) from D. officinale using PCR with degenerate primers, and we have identified a novel type III polyketide synthase (PKS) gene by phylogenetic analyses. In a series of perfect experiments, DoBS1 was expressed in Escherichia coli, purified and some catalytic properties of the recombinant protein were investigated. The molecular weight of the recombinant protein was verified to be approximately 42.7 kDa. An enzyme activity analysis indicated that the recombinant DoBS1-HisTag protein was capable of using 4-coumaryol-CoA and 3 malonyl-CoA as substrates for dihydroresveratrol (DHR) in vitro. The Vmax and Km of the recombinant protein for DHR were 3.57 ± 0.23 nmol·min−1·mg−1 and 0.30 ± 0.08 mmol, respectively. The present study provides further insights into the catalytic mechanism of the active site in the biosynthetic pathway for the catalytic production of dihydroresveratrol by bibenzylase in D. officinale. The results can be used to optimize a novel biosynthetic pathway for the industrial synthesis of DHR.

Alginate oligosaccharides (AOs), derived from alginate degradation, exhibit diverse biological activities and hold significant promise in various fields. The enzymatic preparation of AOs relies on alginate lyases, which offers distinct advantages. In contrast to the conventional use of sodium alginate derived from brown algae as the substrate for the enzymatic preparation of AOs, AO preparation directly from brown algae is more appealing due to its time and energy efficiency. Thus, the identification of potent alginate lyases and cost-effective brown algae substrates is crucial for optimizing AO production. Herein, we identified and characterized an alginate lyase, AlyP18, capable of efficiently decomposing algae, from a marine bacterium Pseudoalteromonas agarivorans A3 based on secretome analysis. AlyP18 is a mesothermal, endo-type and bifunctional alginate lyase with high enzymatic activity. Two brown algae substrates, Laminaria japonica roots and Macrocystis pyrifera, were used for the AO preparation by AlyP18. Upon optimization of AlyP18 hydrolysis parameters, the substrate degradation efficiency and AO production reached 53% and ~32% for L. japonica roots, respectively, and 77% and ~46.5% for M. pyrifera. The generated AOs primarily consisted of dimers to pentamers, with trimers and tetramers being dominant. This study provides an efficient alginate lyase and alternative brown algal feedstock for the bioconversion of high-value AOs from brown algae.

Abstract The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package ‘limma.’ A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable survival prognosis was demonstrated by SDC1 and ITGA2, which were highly expressed during in vitro PDAC cell proliferation, apoptosis, and migration. SDC1 high was enriched in interferon alpha (IFN-α) response and ITGA2 high was primarily detected in epithelial-mesenchymal transition (EMT), which was verified using western blotting. We concluded that SDC1 and ITGA2 are potential prognostic biomarkers for PDAC associated with IPMN. Downregulation of SDC1 and ITGA2 expression in PDAC occurs via a mechanism involving possible regulation of IFN-α response, EMT, and immunity, which may act as new targets for PDAC therapy.

Abstract Background Older adults are underrepresented in research. Heterogeneity of research processes in this population, specifically in long-term care (LTC) and geriatric acute care (GAC), is not well described and may impede the design, planning, and conduct of research. In this study, we identified, quantified, and mapped stakeholders, research stages, and transversal themes of research processes, to develop a mapping framework to improve research capacity by better characterizing this heterogeneity. Methods Multicomponent mixed methods study. An environmental scan was used to initiate a preliminary framework. We conducted a systematic literature search on processes, barriers, and methods for clinical research in GAC and LTC to extract and update stakeholders, research stages, and themes. Importance and interactions of elements were synthesized via heatmaps by number of articles, mentions, and content intersections. Results For our initial framework and environmental scan, we surveyed 24 stakeholders. Of 9277 records, 68 articles were included in our systematic review and allowed us to identify 12 stakeholders, 13 research stages, 17 transversal themes (either barriers, facilitators, general themes, or recommendations), and 1868 intersections. Differences in relative importance between LTC and GAC emerged for stakeholders (staff, managers vs. caregivers, ethics committees), and for research stages (funding, facility recruitment vs. ethics, individual recruitment). Crucial themes according to specific stakeholders were collaboration for the research team; communication, trust, and human resources for managers; heterogeneity for patients and residents. A heatmap framework synthesizing vital stakeholders and themes per research stage was generated. Conclusions We identified and quantified the interactions between stakeholders, stages, and themes to characterize heterogeneity in LTC and GAC research. Our framework may serve as a blueprint to co-construct and improve each stage of the research process.

Abstract Background Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. Results First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. Conclusions Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.

Abstract This study aimed to assess the accuracy of cortical bone trajectory (CBT) screws placement guided by a spinous process clamp (SPC) guide. A total of 32 patients who received single-level midline lumbar fusion (MIDLF) surgery between June 2019 and January 2020 were retrospectively analyzed and divided into free-hand (FH) and SPC-guided groups according to the surgical approach. In the FH group, CBT screws was implanted with the assistance of fluoroscopy, while in the SPC group, CBT screws was implanted using the SPC navigator hardwire. A total of 128 screws were assessed in this study, with higher rates of clinically acceptable screw placement (grades A and B) and grade A screws in the SPC group than in the FH guide group (92.2% vs. 79.7%, P = 0.042 and 54.7% vs. 35.9%, P = 0.033, respectively). Misplacement screws (grades C, D, and E) occurred more often in the FH group than in the SPC guide group (20.3% vs. 7.8%, P = 0.042). The incidence of proximal facet joint violation (FJV) was higher in the FH group than in the SPC group (15.6% vs. 3.1%, P = 0.030). The radiation dose and time in the SPC guide group were comparable to those in the FH group (P = 0.063 and P = 0.078). The average operative time was significantly longer in the SPC guide group than in the FH group (267.8 ± 45.5 min vs. 210.9 ± 44.5 min, P = 0.001). Other clinical parameters, such as the average bone mineral density (BMD), intraoperative blood loss, and postoperative hospital stay, were not significantly different. Oswestry disability index (ODI) and back pain visual analogue scale (VAS) scores were significantly improved in both groups compared with preoperatively. SPC guided screw placement was more accurate than the fluoroscopy-assisted FH technique for single-level MIDLF at L4/5. Patients undergoing SPC-guided screw placement can achieve similar clinical outcomes as the fluoroscopy-assisted FH technique.

Abstract Background Preimplantation genetic testing for aneuploidy (PGT-A) was demonstrated to be superior to conventional IVF in reducing the incidence of miscarriage and abnormal offspring after the first embryo transfer (ET). PGT-A requires several embryo trophectoderm cells, but its negative impacts on embryo development and long-term influence on the health conditions of conceived children have always been a concern. As an alternative, noninvasive PGT-A (niPGT-A) approaches using spent blastocyst culture medium (SBCM) achieved comparable accuracy with PGT-A in several pilot studies. The main objective of this study is to determine whether noninvasive embryo viability testing (niEVT) results in better clinical outcomes than conventional IVF after the first embryo transfer. Furthermore, we further investigated whether niEVT results in higher the live birth rate between women with advanced maternal age (AMA, > 35 years old) and young women or among patients for whom different fertilization protocols are adopted. Methods This study will be a double-blind, multicenter, randomized controlled trial (RCT) studying patients of different ages (20–43 years) undergoing different fertilization protocols (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]). We will enroll 1140 patients at eight reproductive medical centers over 24 months. Eligible patients should have at least two good-quality blastocysts (better than grade 4 CB). The primary outcome will be the live birth rate of the first embryo transfer (ET). Secondary outcomes will include the clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, cumulative live birth rate, ectopic pregnancy rate, and time to pregnancy. Discussion In this study, patients who undergo noninvasive embryo viability testing (niEVT) will be compared to women treated by conventional IVF. We will determine the effects on the pregnancy rate, miscarriage rate, and live birth rate and adverse events. We will also investigate whether there is any difference in clinical outcomes among patients with different ages and fertilization protocols (IVF/ICSI). This trial will provide clinical evidence of the effect of noninvasive embryo viability testing on the clinical outcomes of the first embryo transfer. Trial registration Chinese Clinical Trial Registry (ChiCTR) Identifier: ChiCTR2100051408. 9 September 2021.

Abstract Background Alginate oligosaccharides (AOs) are the degradation products of alginate, a natural polysaccharide abundant in brown algae. AOs generated by enzymatic hydrolysis have diverse bioactivities and show broad application potentials. AOs production via enzymolysis is now generally with sodium alginate as the raw material, which is chemically extracted from brown algae. In contrast, AOs production by direct degradation of brown algae is more advantageous on account of its cost reduction and is more eco-friendly. However, there have been only a few attempts reported in AOs production from direct degradation of brown algae. Results In this study, an efficient Laminaria japonica-decomposing strain Pseudoalteromonas agarivorans A3 was screened. Based on the secretome and mass spectrum analyses, strain A3 showed the potential as a cell factory for AOs production by secreting alginate lyases to directly degrade L. japonica. By using the L. japonica roots, which are normally discarded in the food industry, as the raw material for both fermentation and enzymatic hydrolysis, AOs were produced by the fermentation broth supernatant of strain A3 after optimization of the alginate lyase production and hydrolysis parameters. The generated AOs mainly ranged from dimers to tetramers, among which trimers and tetramers were predominant. The degradation efficiency of the roots reached 54.58%, the AOs production was 33.11%, and the AOs purity was 85.03%. Conclusion An efficient, cost-effective and green process for AOs production directly from the underutilized L. japonica roots by using strain A3 was set up, which differed from the reported processes in terms of the substrate and strain used for fermentation and the AOs composition. This study provides a promising platform for scalable production of AOs, which may have application potentials in industry and agriculture.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05–3.39), 1.62 (1.23–2.12), 2.06 (1.73–2.45), 1.20 (1.16–1.25), and 1.07 (1.05–1.08) per 10 μg/m3 increase in PM2.5, PM2.5–10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33–1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P

Abstract Background Two staging systems, the 8th staging system by the American Joint Committee on Cancer (AJCC) and the 11th Japanese classification by Japan Esophageal Society (JES), are currently applied in the clinic for predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). The differences between the two staging systems have been widely researched. However, little studies focus on the differences in specific staging between the two systems. Therefore, we aimed to compare the performance of different staging in predicting overall survival (OS) of Chinese patients with ESCC. Methods This retrospective study included 268 patients who underwent radical esophagectomy and mediastinal lymph node dissection for ESCC between January 2008 and December 2013. Patients were staged by the 8th AJCC and 11th JES staging systems. OS was estimated using the Kaplan–Meier method and compared between N stages and between stage groupings using the log-rank test. Cox proportional hazards regression analysis was performed to identify factors independently related to outcome. Further, we compared the concordance indexes (C-indexes) of the two staging systems. Results The mean age was 61.25 ± 7.056 years, median follow-up was 44.82 months, and 5-year OS rate was 47%. The OS was well predicted by the 8th AJCC N staging (P

Objective:. Psoriasis is an immune-mediated inflammatory, chronic, recurrent skin disease associated with a high risk of developing psychiatric disorders, especially depression and suicidal ideation, leading to functional disability and poor quality of life. This study was conducted to comprehensively review and assess the epidemiologic association between psoriasis and the risk ratios (RRs) of depression or suicidal ideation. Methods:. Five databases (PubMed, Wanfang Database, CNKI, The Cochrane Library, and EMBASE) were searched for prospective cohort studies on the prevalence of depression and/or suicidal ideation in patients with psoriasis updated to February 2, 2023. Two independent reviewers evaluated and extracted the data, which were then pooled into a summary RR with corresponding 95% confidence interval (CI) using random-effects models. Results:. Sixteen cohort studies comprising 1,166,840 patients with psoriasis and 3,294,205 controls were eligible for the final analysis. The pooled RR for depression was 1.43 (95% CI = 1.13–1.81) in patients with psoriasis and1.55 (95% CI = 1.40–1.71) in patients with psoriatic arthritis. In the subgroup analysis, Asian patients with psoriasis (RR = 1.38, 95% CI =1.17–1.63) had a lower pooled RR for depression than non-Asian patients (RR = 1.45, 95% CI = 1.07–1.97), and patients with moderate-to-severe psoriasis (RR = 1.69, 95% CI = 1.15–2.50) showed a higher RR for depression than patients with mild psoriasis (RR = 1.60, 95% CI = 1.06–2.42). We also found no increase in the RR for suicidal ideation among people with psoriasis (RR = 1.25, 95% CI = 0.95–1.65). Conclusion:. Patients with psoriasis are at an increased risk of depression. Among patients with psoriasis, those with psoriatic arthritis, those who are non-Asian, and those with moderate-to-severe psoriasis are at higher risk for depression. However, the available evidence does not support an association between psoriasis and suicidal ideation.