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The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.

Identifying cells of tumor origin is a fundamental question in tumor biology. Answers to this central question will not only advance our understanding of tumor initiation and progression but also have important therapeutic implications. In this study, we a

Data acquisition for transcriptomic studies used to be the bottleneck in the transcriptomic analytical pipeline. However, recent developments in transcriptome profiling technologies have increased researchers' ability to obtain data, resulting in a shift in focus to data analysis. Incorporating machine learning to traditional analytical methods allows the possibility of handling larger volumes of complex data more efficiently. Many bioinformaticians, especially those unfamiliar with ML in the study of human transcriptomics and complex biological systems, face a significant barrier stemming from their limited awareness of the current landscape of ML utilisation in this field. To address this gap, this review endeavours to introduce those individuals to the general types of ML, followed by a comprehensive range of more specific techniques, demonstrated through examples of their incorporation into analytical pipelines for human transcriptome investigations. Important computational aspects such as data pre-processing, task formulation, results (performance of ML models), and validation methods are encompassed. In hope of better practical relevance, there is a strong focus on studies published within the last five years, almost exclusively examining human transcriptomes, with outcomes compared with standard non-ML tools., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Long-read sequencing technologies can capture entire RNA transcripts in a single sequencing read, reducing the ambiguity in constructing and quantifying transcript models in comparison to more common and earlier methods, such as short-read sequencing. Recent improvements in the accuracy of long-read sequencing technologies have expanded the scope for novel splice isoform detection and have also enabled a far more accurate reconstruction of complex splicing patterns and transcriptomes. Additionally, the incorporation and advancements of machine learning and deep learning algorithms in bioinformatic software have significantly improved the reliability of long-read sequencing transcriptomic studies. However, there is a lack of consensus on what bioinformatic tools and pipelines produce the most precise and consistent results. Thus, this review aims to discuss and compare the performance of available methods for novel isoform discovery with long-read sequencing technologies, with 25 tools being presented. Furthermore, this review intends to demonstrate the need for developing standard analytical pipelines, tools, and transcript model conventions for novel isoform discovery and transcriptomic studies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Transformation of carbon dioxide and nitrate ions into urea offers an attractive route for both nitrogen fertilizer production and environmental remediation. However, achieving this transformation under mild conditions remains challenging. Herein, we report an efficient photoelectrochemical method for urea synthesis by co-reduction of carbon dioxide and nitrate ion over a Cu 2 O photocathode, delivering urea formation rate of 29.71±2.20 μmol g -1  h -1 and Faradaic efficiency (FE) of 12.90±1.15 % at low external potential (-0.017 V vs. reversible hydrogen electrode). Experimental data combined with theoretical calculations suggest that the adsorbed CO* and NO 2 * species are the key intermediates, and associated C-N coupling is the rate-determining step. This work demonstrates that Cu 2 O is an efficient catalyst to drive co-reduction of CO 2 and NO 3 - to urea under light irradiation with low external potential, showing great opportunity of photoelectrocatalysis as a sustainable tool for value-added chemical synthesis., (© 2024 Wiley-VCH GmbH.)

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d , featuring an 8a- N -acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3 , but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N -acylhydrazone to enhance drug-like properties.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli., Competing Interests: Competing interests statement:The authors declare no competing interest.

Circular RNAs (circRNAs) are a subclass of non-coding RNAs which have demonstrated potential as biomarkers for Alzheimer's disease (AD). In this study, we conducted a comprehensive exploration of the circRNA transcriptome within AD brain tissues. Specifically, we assessed circRNA expression patterns in the dorsolateral prefrontal cortex collected from nine AD-afflicted individuals and eight healthy controls. Utilising two circRNA detection tools, CIRI2 and CIRCexplorer2, we detected thousands of circRNAs and performed a differential expression analysis. CircRNAs which exhibited statistically significantly differential expression were identified as AD-specific differentially expressed circRNAs. Notably, our investigation revealed 120 circRNAs with significant upregulation and 1325 circRNAs displaying significant downregulation in AD brains when compared to healthy brain tissue. Additionally, we explored the expression profiles of the linear RNA counterparts corresponding to differentially expressed circRNAs in AD-afflicted brains and discovered that the linear RNA counterparts exhibited no significant changes in the levels of expression. We used CRAFT tool to predict that circUBE4B had potential to target miRNA named as hsa-miR-325-5p, ultimately regulated CD44 gene. This study provides a comprehensive overview of differentially expressed circRNAs in the context of AD brains, underscoring their potential as molecular biomarkers for AD. These findings significantly enhance our comprehension of AD's underlying pathophysiological mechanisms, offering promising avenues for future diagnostic and therapeutic developments., (© 2024. The Author(s).)

Hydrogels are considered as a potential cartilage replacement material based on their structure being similar to natural cartilage, which are of great significance in repairing cartilage defects. However, it is difficult for the existing hydrogels to combine the high load bearing and low friction properties (37 °C) of cartilage through sample methods. Herein, we report a facile and new fabrication strategy to construct the PNIPAm/EYL hydrogel by using the macrophase separation of supersaturated N -isopropylacrylamide (NIPAm) monomer solution to promote the formation of liposomes from egg yolk lecithin (EYL) and asymmetric template method. The PNIPAm/EYL hydrogels possess a relatively high compressive strength (more than 12 MPa), fracture energy (9820 J/m 2 ), good fatigue resistance, lubricating properties, and excellent biocompatibility. Compared with the PNIPAm hydrogel, the friction coefficient (COF 0.046) of PNIPAm/EYL hydrogel is reduced by 50%. More importantly, the COF (0.056) of PNIPAm/EYL hydrogel above lower critical solution temperature (LCST) does not increase significantly, exhibiting heat-tolerant lubricity. The finite element analysis further proves that PNIPAm/EYL hydrogel can effectively disperse the applied stress and dissipate energy under load conditions. This work not only provides new insights for the design of high-strength lubricating hydrogels but also lays a foundation for the treatment of cartilage injury as a substitute material.

We conducted a retrospective cohort analysis to examine the association between hemoglobin (Hb) levels and refracture risk in elderly patients with osteoporotic fractures (OPFs). Our findings suggest a nonlinear relationship exists in females, and females with Hb levels below 10.7 g/dL may be at a higher risk of refracture., Introduction: Hematopoiesis and bone health have a reciprocal influence on each other. Nevertheless, there is a scarcity of in-depth research on the association between Hb levels and the occurrence of fractures. The present research aimed to investigate the correlation between Hb levels and the rate of refracture within 5 years among individuals with OPFs., Methods: A retrospective cohort analysis was undertaken between 2017 and 2022. The study included 1906 individuals who were inhabitants of Kunshan and were over 60 years old. These individuals had experienced an OPF between January 1, 2017, and July 27, 2022, resulting in their hospitalization. Cox proportional hazard regression models were used to evaluate the risk of refracture within 5 years based on the Hb levels acquired during the admission examination, with consideration for sex differences. A nonlinear relationship was identified using smoothed curve fitting and threshold analysis. Kaplan-Meier curves were used to compare refracture rates between patients with low and high Hb levels., Results: Elderly female patients with OPFs and lower Hb levels exhibited a significantly higher risk of a 5-year refracture. Conversely, no significant associations were observed between the two variables in male patients. A nonlinear correlation was found between Hb levels and the probability of refracture in females, with a turning point identified at 10.7 g/dL of Hb levels. A strong negative association was observed with the five-year refracture rate when Hb levels fell below 10.7 g/dL (hazard ratio (HR) = 0.63; 95% confidence interval (CI) 0.48 to 0.83; P-value = 0.0008). This finding suggests that for every 1 g/dL increase in Hb below 10.7 g/dL, the risk of refracture reduced by 37%. However, no statistically significant association was observed when Hb levels were above 10.7 g/dL., Conclusions: The findings demonstrated a significant negative correlation between Hb levels and the likelihood of refracture in elderly female patients with OPFs and suggested that elderly females with recent OPFs and Hb levels below 10.7 g/dL may be at a higher risk of refracture. Additionally, the Hb levels can serve as an indicator of bone fragility in elderly female patients with OPFs. These findings highlight the importance of monitoring Hb levels as a part of comprehensive management strategies to both assess skeletal health and prevent refractures in this population., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

The precise control of spin states in transition metal (TM)-based single-atom catalysts (SACs) is crucial for advancing the functionality of electrocatalysts, yet it presents significant scientific challenges. Using density functional theory (DFT) calculations, we propose a novel mechanism to precisely modulate the spin state of the surface-adsorbed Fe atom on the MoS 2 bilayer. This is achieved by strategically intercalating a TM atom into the interlayer space of the MoS 2 bilayer. Our results show that these strategically intercalated TM atoms can induce a substantial interfacial charge polarization, thereby effectively controlling the charge transfer and spin polarization on the surface Fe site. In particular, by varying the identity of the intercalated TM atoms and their vacancy filling site, a continuous modulation of the spin states of the surface Fe site from low to medium to high can be achieved, which can be accurately described using descriptors composed of readily accessible intrinsic properties of materials. Using the electrochemical dinitrogen reduction reaction (eNRR) as a prototypical reaction, we discovered a universal volcano-like relation between the tuned spin and the catalytic activity of Fe-based SACs. This finding contrasts with the linear scaling relationships commonly seen in traditional studies and offers a robust new approach to modulating the activity of SACs through interfacial engineering., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Gene fusions have had a significant role in the development of various types of cancer, oftentimes involved in oncogenic activities through dysregulation of gene expression or signalling pathways. Some cancer-associated chromosomal translocations can undergo backsplicing, resulting in fusion-circular RNAs, a more stable isoform immune to RNase degradation. This stability makes fusion circular RNAs a promising diagnostic biomarker for cancer. While the detection of linear fusion RNAs and their function in certain cancers have been described in literature, fusion circular RNAs lag behind due to their low abundance in cancer cells. This review highlights current literature on the role of linear and circular fusion transcripts in cancer, tools currently available for detecting of these chimeric RNAs and their function and how they play a role in tumorigenesis., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Improving the efficiency of the oxygen evolution reaction (OER) is crucial for advancing sustainable and environmentally friendly hydrogen energy. Layered double hydroxides (LDHs) have emerged as promising electrocatalysts for the OER. However, a thorough understanding of the impact of structural disorder and defects on the catalytic activity of LDHs remains limited. In this work, a series of NiAl-LDH models are systematically constructed, and their OER performance is rigorously screened through theoretical density functional theory. The acquired results unequivocally reveal that the energy increase induced by structural disorder is effectively counteracted at the defect surface, indicating the coexistence of defects and disorder. Notably, it is ascertained that the simultaneous presence of defects and disorder synergistically augments the catalytic activity of LDHs in the context of the OER. These theoretical findings offer valuable insights into the design of highly efficient OER catalysts while also shedding light on the efficacy of LDH electrocatalysts.

Hyperactivated KRAS mutations fuel tumorigenesis and represent attractive targets for cancer treatment. While covalent inhibitors have shown clinical benefits against the KRAS G12C mutant, advancements for non-G12C mutants remain limited, highlighting the urgent demand for pan-KRAS inhibitors. RNA G-quadruplexes (rG4s) in the 5'-untranslated region of KRAS mRNA can regulate KRAS translation, making them promising targets for pan-KRAS inhibitor development. Herein, we designed and synthesized 50 novel coumarin-quinolinium derivatives, leveraging our previously developed rG4-specific ligand, QUMA-1 . Notably, several compounds exhibited potent antiproliferative activity against cancer cells as pan-KRAS translation inhibitors. Among them, 15a displayed exceptional capability in stabilizing KRAS rG4s, suppressing KRAS translation, and consequently modulating MAPK and PI3K-AKT pathways. 15a induced cell cycle arrest, prompted apoptosis in KRAS-driven cancer cells, and effectively inhibited tumor growth in a KRAS mutant xenograft model. These findings underscore the potential of 15a as a pan-KRAS translation inhibitor, offering a novel and promising approach to target various KRAS-driven cancers.

Background: Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging., Methods: A tumour necrosis factor (TNF)-α-induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)-treated 8-week-old model mice and 23-month-old (aged) mice were used to examine the therapeutic effects of handelin on cachexia- and aging-induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis., Results: Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF-α-induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin-like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin-1 expression, inhibited nuclear factor-κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS-treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross-sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti-inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant-related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL-1β levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy., Conclusions: Handelin ameliorated cachexia- and aging-induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

This study describes a new species of Pinnularia , P.hupingensis sp. nov. , on the basis of light and scanning electron microscope images. Pinnulariahupingensis sp. nov. is characterised by its linear valve outline, extremely divergent striae, and very large hexagonal central area occupying ca. 1/5-1/8 of the valve length. The primary and secondary sides of the valve and the internal proximal raphe fissures are discussed. The new species is compared to similar taxa of the genus Pinnularia ., Competing Interests: The authors have declared that no competing interests exist., (San-Mei Xu, Bing Liu, Patrick Rioual, Man-Qi Yi, Yi-Dan Ma.)

Background: Few studies have examined the relationship between perioperative blood transfusion (PBT) and length of hospital stay (LOS) in patients with osteoporotic fractures. This research aims to study the association between PBT and LOS., Methods: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China, involving 2357 osteoporotic fractures (OPF) patients who received surgical treatment during hospitalization from January 2017 and March 2022. Multiple linear regression was used to analyze the relationship between PBT and LOS. In the analysis, PBT volume was the dependent variable, whereas LOS was the independent variable. Simultaneously, age, gender, body mass index, hemoglobin, primary diagnosis, American Society of Anesthesiologists, creatinine (Cr), anesthesia, surgical method, and Charlson comorbidity index were included as covariates. The generalized additive model was then used to study nonlinear associations. Two piecewise linear regression exemplary evaluated the inception results for smoothing the curve., Results: Our results proved that PBT was positively correlated with LOS in the fully adjusted model (β, 0.21; 95% CI, 0.04 to 0.37; P < 0.0001). Furthermore, a "U-shape" nonlinear relationship existed between PBT and LOS. When the concentration of PBT was between 0 and 1.5 units, it was manifested as a negative correlation between PBT and LOS. However, there was a positive association between PBT and LOS when PBT levels exceeded 1.5 units., Conclusions: This study demonstrated that PBT and LOS in the OPF population were independent with a nonlinear relationship. These results suggest that PBT may be protective for patients with long LOS. If these findings are confirmed, the LOS in OPF patients can be regulated through appropriate perioperative blood transfusion., (© 2023. The Author(s).)

Mammals have limited capacity for heart regeneration, whereas zebrafish have extraordinary regeneration abilities. During zebrafish heart regeneration, endothelial cells promote cardiomyocyte cell cycle reentry and myocardial repair, but the mechanisms responsible for promoting an injury microenvironment conducive to regeneration remain incompletely defined. Here, we identify the matrix metalloproteinase Mmp14b as an essential regulator of heart regeneration. We identify a TEAD-dependent mmp14b endothelial enhancer induced by heart injury in zebrafish and mice, and we show that the enhancer is required for regeneration, supporting a role for Hippo signaling upstream of mmp14b . Last, we show that MMP-14 function in mice is important for the accumulation of Agrin, an essential regulator of neonatal mouse heart regeneration. These findings reveal mechanisms for extracellular matrix remodeling that promote heart regeneration.

Obesity, a global pandemic posing a growing threat to human health, necessitates the development of effective and safe anti-obesity agents. Our previous studies highlighted the lipid-lowering effects of indolylquinazoline Bouchardatine and its derivatives. In this study, we employed scaffold hopping and simplification strategies to design and synthesize two new series derivatives by modifying the D ring. Extensive discussions have been conducted regarding the structure-activity relationship between lipid-lowering activity and the new compounds. These discussions have resulted in the discovery of 2-pyrimidinylindole derivatives as a promising scaffold for anti-obesity treatment. The new 2-pyrimidinylindole derivatives exhibited comparable lipid-lowering activity to the previously reported indolylquinazoline derivatives, including SYSU-3d and R17, with reduced toxicity. The most potent compound, 5a, demonstrated a larger therapeutic index, improved aqueous solubility and oral bioavailability compared to the previous lead compounds. In vivo evaluation indicated that 5a effectively reduced lipid accumulation in adipose tissue, improved glucose tolerance, and mitigated insulin resistance and liver function damage caused by a high-fat and high-cholesterol diet. Mechanism studies indicated that 5a may regulate lipid metabolism through the modulation of the PPARγ signaling pathway. Overall, our study has identified a highly active compound 5a, and provided the basis for further development of 2-pyrimidinylindole as a promising scaffold for obesity treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: The cap-snatching mechanism of influenza virus mRNA transcription is strongly suppressed by TG-1000, a prodrug rapidly metabolized into TG-0527, is a potent cap-dependent nucleic acid endonuclease inhibitor. Herein, we aimed to assess the safety, tolerability, and pharmacokinetics of TG-1000 in healthy participants and the effect of food on the pharmacokinetics and safety of TG-1000. Method: The study was divided into 2 parts: Part A [Single Ascending-Dose (SAD) study, 10-160 mg] and Part B [Food-Effect (FE) study, 40 mg] were launched sequentially. The study included 66 participants for both investigations. We administered different TG-1000 capsules or placebo doses per the study protocol and collected blood samples for pharmacokinetic assessments at specific times. In plasma, TG-1000 and its active metabolite TG-0527 were assayed, and PK parameters were determined. Results: In SAD, the increase in AUC was less than the proportional increase in dose over the 20-160 mg dose range, while the increase in C max was proportional to the increase in dose. In the 10-160 mg dose range, T 1/2 , λz and T max of TG-0527 were dose-independent; and T 1/2 and T max were within 33.8-39.4 h and 3.02-6 h, respectively. In FE, the AUC 0-inf , AUC 0-last , and C max of TG-0527 decreased by approximately 17.52%, 18.76%, and 41.35%, respectively, and the T max delay was around 1.50 h. No serious adverse events occurred during the studies. Conclusion: Overall, TG-1000 was well tolerated and exhibited an acceptable safety and PK profile, supporting further clinical investigation of TG-1000 for the treatment of influenza., Competing Interests: Authors L-WC, C-YT were employed by TaiGen Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Chang, Tsai, Liu, Li, Li, Li and Xu.)

Osteoporosis (OP) is often associated with other complications, such as impaired glucose homeostasis. Vitamin D deficiency is common and has been linked to bone metabolism and the regulation of blood sugar levels. The aim of this study was to evaluate the independent relationship between serum 25-hydroxyvitamin D (25[OH]D) and fasting blood glucose levels (FBG) in a group of patients diagnosed with OP. This is a retrospective cross-sectional study from a prospectively collected database at our tertiary referral center. Consecutive 2084 OP patients who were hospitalization were finally analyzed in this study. FBG is the dependent variable, serum 25(OH)D level of OP patients is exposure variable of this study. There was a linear significantly negative association between serum 25(OH)D and FBG (β, - 0.02; 95% CI - 0.03 to - 0.01; P = 0.0011) in the fully adjusted models. Specifically, when serum 25(OH)D level was less than 23.39 ng/mL, FBG decreased by 0.04 mmol/L for every 1 ng/mL increase of serum 25(OH)D level. When serum 25(OH)D was greater than 23.39 ng/ mL, the negative association was insignificant (P = 0.9616). If the association is confirmed, the clinical management of blood glucose in OP patients with serum 25(OH)D deficiency has instructive implications., (© 2023. The Author(s).)

We compared newly developed delayed-release oral tablets (test) of 30-mg nifedipine (NFP) with its marketed counterpart (30 mg; reference) in healthy adult Chinese volunteers to assess the former's bioequivalence. This was a randomized, open-label, four-period, crossover trial study including fasting and fed trials. The participants were randomly administered test or reference formulations (1:1 ratio) throughout each period, with a 7-day washout period. In the next session, they were administered the alternate products. Liquid chromatography-tandem mass spectrometry and WinNonlin software were used to evaluate the bioequivalence of the maximum plasma concentration (C max ) of NFP and the area under the concentration-time curve (AUC). In total, 46 and 48 people participated in the fasting and postprandial trials. In both groups, the 90% confidence intervals of geometric mean ratios of C max , AUC from time zero to time t, and AUC from time zero to infinity were in the equivalence range (80%-125%). When NFP was administered concomitantly with a high-fat meal, time to maximum concentration was approximately twofold earlier, absorption was approximately 4.8% less, and C max exhibited a slight change relative to those under fasting conditions. Moreover, no serious adverse events were recorded in the participants. The present findings confirm the bioequivalence of test and reference formulations of NFP tablets under fasting and postprandial conditions., (© 2023, The American College of Clinical Pharmacology.)

Background: Nonalcoholic fatty liver disease (NAFLD) has become a global health issue owing to its large disease population and high morbidity. We previously reported that the improvement in oxidative stress (OS) using pure total flavonoids from citrus (PTFC), flavonoids isolated from the peel of Citrus changshan-huyou Y.B. Chan, is a crucial strategy for NAFLD treatment. However, OS-associated intervention pathways in NAFLD remain unclear., Methods: In this study, we used microRNA (miR)- and mRNA-sequencing to identify the pathway by which PTFC improve OS in NAFLD. Clinical data, mimic/inhibitor assays, and a dual-luciferase reporter assay were selected to verify the regulatory relationships of this pathway. Moreover, in vivo and in vitro experiments were used to confime the regulatory effect of PTFC on this pathway., Results: miR-seq, mRNA-seq, and bioinformatics analyses revealed that the miR-137-3p/neutrophil cytosolic factor 2 (NCF2, also known as NOXA2)/cytochrome b-245 beta chain (CYBB, also known as NOX2) pathway may be a target pathway for PTFC to improve OS and NAFLD. Additionally, bivariate logistic regression analysis combining the serum and clinical data of patients revealed NOX2 and NOXA2 as risk factors and total antioxidant capacity (indicator of OS level) as a protective factor for NAFLD. miR-137-3p mimic/inhibitor assays revealed that the upregulation of miR-137-3p is vital for improving cellular steatosis, OS, and inflammation. Dual-luciferase reporter assay confirmed that NOXA2 acts as an miR-137-3p sponge. These results co-determined that miR-137-3p/NOXA2/NOX2 is an essential pathway involved in NAFLD pathogenesis, including lipid accumulation, OS, and inflammation. In vivo and in vitro experiments further confirmed that the miR-137-3p/NOXA2/NOX2 pathway is regulated by PTFC., Conclusion: PTFC alleviates OS and inflammation in NAFLD by regulating the miR-137-3p/NOXA2/NOX2 pathway., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with obscure aetiology. The underdiagnosis rate of ME/CFS is high due to the lack of diagnostic criteria based on objective markers. In recent years, circRNAs have emerged as potential genetic biomarkers for neurological diseases, including Parkinson's disease and Alzheimer's disease, making them likely to have the same prospect of being biomarkers in ME/CFS. However, despite the extensive amount of research that has been performed on the transcriptomes of ME/CFS patients, all of them are solely focused on linear RNAs, and the profiling of circRNAs in ME/CFS has been completely omitted. In this study, we investigated the expression profiles of circRNAs, comparing ME/CFS patients and controls before and after two sessions of cardiopulmonary exercise longitudinally. In patients with ME/CFS, the number of detected circRNAs was higher compared to healthy controls, indicating potential differences in circRNA expression associated with the disease. Additionally, healthy controls showed an increase in the number of circRNAs following exercise testing, while no similar pattern was evident in ME/CFS patients, further highlighting physiological differences between the two groups. A lack of correlation was observed between differentially expressed circRNAs and their corresponding coding genes in terms of expression and function, suggesting the potential of circRNAs as independent biomarkers in ME/CFS. Specifically, 14 circRNAs were highly expressed in ME/CFS patients but absent in controls throughout the exercise study, indicating a unique molecular signature specific to ME/CFS patients and providing potential diagnostic biomarkers for the disease. Significant enrichment of protein and gene regulative pathways were detected in relation to five of these 14 circRNAs based on their predicted miRNA target genes. Overall, this is the first study to describe the circRNA expression profile in peripheral blood of ME/CFS patients, providing valuable insights into the molecular mechanisms underlying the disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In the literature, scarce data investigate the link between 25-hydroxyvitamin D (25[OH]D) and blood lipids in the osteoporosis (OP) population. 25(OH)D, as a calcium-regulating hormone, can inhibit the rise of parathyroid hormone, increase bone mineralization to prevent bone loss, enhance muscle strength, improve balance, and prevent falls in the elderly. This retrospective cross-sectional study aimed to investigate the association between serum 25(OH)D levels and lipid profiles in patients with osteoporosis, with the objective of providing insight for appropriate vitamin D supplementation in clinical settings to potentially reduce the incidence of cardiovascular disease, which is known to be a major health concern for individuals with osteoporosis., Methods: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, including 2063 OP patients who received biochemical blood analysis of lipids during hospitalization from January 2015 to March 2022. The associations between serum lipids and 25(OH)D levels were examined by multiple linear regression. The dependent variables in the analysis were the concentrations of serum lipoprotein, total cholesterol (TC), triglycerides (TGs), apolipoprotein-A, lipoprotein A, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C). The independent variable was the concentration of blood serum 25(OH)D. At the same time, age, body mass index, sex, time and year of serum analysis, primary diagnosis, hypertension, diabetes, statins usage, beta-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide were covariates. Blood samples were collected in the early morning after the overnight fasting and were analyzed using an automated electrochemiluminescence immunoassay on the LABOSPECT 008AS platform (Hitachi Hi-Tech Co., Ltd., Tokyo, Japan). The generalized additive model was further applied for nonlinear associations. The inception result for smoothing the curve was evaluated by two-piecewise linear regression exemplary., Results: Our results proved that in the OP patients, the serum 25(OH)D levels were inversely connected with blood TGs concentration, whereas they were positively associated with the HDL, apolipoprotein-A, and lipoprotein A levels. In the meantime, this research also found a nonlinear relationship and threshold effect between serum 25(OH)D and TC, LDL-C. Furthermore, there were positive correlations between the blood serum 25(OH)D levels and the levels of TC and LDL-C when 25(OH)D concentrations ranged from 0 to 10.04 ng/mL. However, this relationship was not present when 25(OH)D levels were higher than 10.04 ng/mL., Conclusions: Our results demonstrated an independent relationship between blood lipids and vitamin D levels in osteoporosis patients. While we cannot establish a causal relationship between the two, our findings suggest that vitamin D may have beneficial effects on both bone health and blood lipid levels, providing a reference for improved protection against cardiovascular disease in this population. Further research, particularly interventional studies, is needed to confirm these associations and investigate their underlying mechanisms., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB -/- bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH., (© 2023. The Author(s).)

Introducing different active sites into heterogeneous catalysts provides new prospects to address the challenges in single-atom catalysis. Herein, the Au single atoms together and the Au nanoparticles were loaded onto NiAl-LDH by a facile impregnation-reduction method for the first time, resulting in the formation of Au 1+ n -NiAl-LDH, in which abundant Au single atoms are located around the Au nanoparticles with ∼5 nm size. When applied in the electrocatalytic benzyl alcohol oxidation reaction (BAOR), the as-prepared Au 1+ n -NiAl-LDH exhibits a remarkable selectivity of 91% and 177.63 μmol for benzaldehyde in 5 hours, while in contrast examples using solely Au single atom loaded NiAl-LDH (Au 1 -NiAl-LDH) and solely Au nanoparticle loaded NiAl-LDH (Au n -NiAl-LDH) can only realize 87.36 μmol production (75% selectivity) and 48.90 μmol production (28% selectivity) of benzaldehyde, respectively. Such a dramatic difference can be attributed to the synergistic effects of Au single atoms and Au nanoparticles. DFT calculation results reveal that for Au 1+ n -NiAl-LDH, Au single atoms promote the dehydrogenation capacity of LDH laminates, while Au nanoparticles offer adsorption sites for the electrophilic attachment of benzyl alcohol.

Metabolic reprogramming is a crucial hallmark of tumorigenesis. Modulating the reprogrammed energy metabolism is an attractive anticancer therapeutic strategy. We previously found a natural product, bouchardatine , modulated aerobic metabolism and inhibited proliferation in the colorectal cancer cell (CRC). Herein, we designed and synthesized a new series of bouchardatine derivatives to discover more potential modulators. We applied the dual-parametric high-content screening (HCS) to evaluate their AMP-activated protein kinase (AMPK) modulation and CRC proliferation inhibition effect simultaneously. And we found their antiproliferation activities were highly correlated to AMPK activation. Among them, 18a was identified with nanomole-level antiproliferation activities against several CRCs. Interestingly, the evaluation found that 18a selectively upregulated oxidative phosphorylation (OXPHOS) and inhibited proliferation by modulating energy metabolism. Additionally, this compound effectively inhibited the RKO xenograft growth along with AMPK activation. In conclusion, our study identified 18a as a promising candidate for CRC treatment and suggested a novel anti-CRC strategy by AMPK activating and OXPHOS upregulating.

Background: The results of studies exploring the association between serum uric acid (SUA) and bone mineral density (BMD) have been controversial and inconsistent. We thus sought to explore whether SUA levels were independently associated with BMD in patients with osteoporosis (OP)., Methods: This cross-sectional analysis was conducted using prospectively obtained data from the Affiliated Kunshan Hospital of Jiangsu University database pertaining to 1,249 OP patients that were hospitalized from January 2015 - March 2022. BMD was the outcome variable for this study, while baseline SUA levels were the exposure variable. Analyses were adjusted for a range of covariates including age, gender, body mass index (BMI) and a range of other baseline laboratory and clinical findings., Results: SUA levels and BMD were independently positively associated with one another in OP patients. Following adjustment for age, gender, BMI, blood urae nitrogen (BUN), and 25(OH)D levels, a 0.0286 g/cm 2 (β, 0.0286; 95% confidence interval [CI], 0.0193-0.0378, P < 0.000001) increase in BMD was observed per 100 μmol/L rise in SUA levels. A non-linear association between SUA and BMD was also observed for patients with a BMI < 24 kg/m 2 , with a SUA level inflection point at 296 μmol/L in the adjusted smoothed curve., Conclusions: These analyses revealed SUA levels to be independently positively associated with BMD in OP patients, with an additional non-linear relationship between these two variables being evident for individuals of normal or low body weight. This suggests that SUA levels may exert a protective effect on BMD at concentrations below 296 μmol/L in normal- and low-weight OP patients, whereas SUA levels above this concentration were unrelated to BMD., (© 2023. The Author(s).)

Background: Among primary brain tumors, gliomas are associated with a poor prognosis and a median survival that varies depending on the tumor grade and subtype. As the most malignant form of glioma, glioblastoma (GBM) constitutes a significant health concern. Alteration in granulin(GRN) has been proved to be accountable for several diseases. However, the relationship between GRN and GBM remains unclear. We evaluated the role of GRN in GBM through The Cancer Genome Atlas (TCGA) database., Methods: First, we assessed the relationship between GRN and GBM through the GEPIA database. Next, the relationship between GRN and GBM prognosis was analyzed by logistic regression and multivariate cox methods. Using CIBERSORT and the GEPIA correlation module, we also investigated the link between GRN and immune infiltrates in cancer. Using the TCGA data, a gene set enrichment analysis (GSEA) was performed. We also employed Tumor Immune Estimation Resource (TIMER) to examine the data set of GRN expression and immune infiltration level in GBM and investigate the cumulative survival in GBM. We also validated tissues from GBM patients by Western blotting, RT-qPCR, and immunohistochemistry., Results: Increased GRN expression was shown to have a significant relationship to tumor grade in a univariate study utilizing logistic regression. Furthermore, multivariate analysis disclosed that GRN expression down-regulation is an independent predictive factor for a favorable outcome. GRN expression level positively correlates with the number of CD4+ T cells, neutrophils, macrophages, and dendritic cells (DCs) that infiltrate a GBM. The GSEA also found that the high GRN expression phenotype pathway was enriched for genes involved in immune response molecular mediator production, lymphocyte-mediated immunity, cytokine-mediated signaling pathway, leukocyte proliferation, cell chemotaxis, and CD4+ alpha beta T cell activation. Differentially enriched pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) include lysosome, apoptosis, primary immunodeficiency, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and B cell receptor signaling pathway. Validated result showed that GRN was upregulated in GBM tissues. These results suggested that GRN was a potential indicator for the status of GBM., Conclusion: GRN is a prognostic biomarker and correlated with immune infiltrates in GBM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Xiao, Hu, Zhong, Zeng, Wu, Li and Song.)

Transition-metal-based oxyhydroxides are efficient catalysts in biomass electrooxidation towards fossil-fuel-free production of valuable chemicals. However, identification of active sites remains elusive. Herein, using cobalt oxyhydroxide (CoOOH) as the archetype and the electrocatalyzed glucose oxidation reaction (GOR) as the model reaction, we track dynamic transformation of the electronic and atomic structure of the catalyst using a suite of operando and ex situ techniques. We reveal that two types of reducible Co 3+ -oxo species are afforded for the GOR, including adsorbed hydroxyl on Co 3+ ion (μ 1 -OH-Co 3+ ) and di-Co 3+ -bridged lattice oxygen (μ 2 -O-Co 3+ ). Moreover, theoretical calculations unveil that μ 1 -OH-Co 3+ is responsible for oxygenation, while μ 2 -O-Co 3+ mainly contributes to dehydrogenation, both as key oxidative steps in glucose-to-formate transformation. This work provides a framework for mechanistic understanding of the complex near-surface chemistry of metal oxyhydroxides in biomass electrorefining., (© 2023 Wiley-VCH GmbH.)

Transformation of biomass and plastic wastes to value-added chemicals and fuels is considered an upcycling process that is beneficial to resource utilization. Electrocatalysis offers a sustainable approach; however, it remains a huge challenge to increase the current density and deliver market-demanded chemicals with high selectivity. Herein, we demonstrate an electrocatalytic strategy for upcycling glycerol (from biodiesel byproduct) to lactic acid and ethylene glycol (from polyethylene terephthalate waste) to glycolic acid, with both products being as valuable monomers for biodegradable polymer production. By using a nickel hydroxide-supported gold electrocatalyst (Au/Ni(OH) 2 ), we achieve high selectivities of lactic acid and glycolic acid (77 and 91%, respectively) with high current densities at moderate potentials (317.7 mA/cm 2 at 0.95 V vs RHE and 326.2 mA/cm 2 at 1.15 V vs RHE, respectively). We reveal that glycerol and ethylene glycol can be enriched at the Au/Ni(OH) 2 interface through their adjacent hydroxyl groups, substantially increasing local concentrations and thus high current densities. As a proof of concept, we employed a membrane-free flow electrolyzer for upcycling triglyceride and PET bottles, attaining 11.2 g of lactic acid coupled with 9.3 L of H 2 and 13.7 g of glycolic acid coupled with 9.4 L of H 2 , respectively, revealing the potential of coproduction of valuable chemicals and H 2 fuel from wastes in a sustainable fashion.

Background: Femoral trochlear dysplasia (FTD) is an important risk factor for patellar instability. Dejour classification is widely used at present and relies on standard lateral X-rays, which are not common in clinical work. Therefore, magnetic resonance imaging (MRI) has become the first choice for the diagnosis of FTD. However, manually measuring is tedious, time-consuming, and easily produces great variability., Aim: To use artificial intelligence (AI) to assist diagnosing FTD on MRI images and to evaluate its reliability., Methods: We searched 464 knee MRI cases between January 2019 and December 2020, including FTD ( n = 202) and normal trochlea ( n = 252). This paper adopts the heatmap regression method to detect the key points network. For the final evaluation, several metrics (accuracy, sensitivity, specificity, etc .) were calculated., Results: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the AI model ranged from 0.74-0.96. All values were superior to junior doctors and intermediate doctors, similar to senior doctors. However, diagnostic time was much lower than that of junior doctors and intermediate doctors., Conclusion: The diagnosis of FTD on knee MRI can be aided by AI and can be achieved with a high level of accuracy., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chiral supramolecular assembly (CSA) based on achiral molecules has provided important clues to understand the origin of biological chirality. However, a simple achiral monomer faces the challenge of chiral stacking with the absence of a chiral resource. The difficulty is that simple achiral monomer lacks steric repulsion to provide asymmetry during hierarchical assembly, which is a prerequisite for chiral stacking with an angle. Moreover, during chiral stacking of achiral molecules or units, the right-handed and left-handed chiral supramolecular isomers (CSIs) are equally formed due to the mirror-imaged conformation, which leads to chirality silence. Here, with the benefit of two-dimensional confinement space of layered double hydroxide (LDH), simple achiral molecules can be arranged to staggered bilayer arrays by imprinting the topological structure of LDH. Once LDH is removed, these staggered arrays can form asymmetric living seeds, which can further elongate to living units with the advantage of living supramolecular polymerization (LSP) by following off-pathway. Due to the asymmetry of living units, the possible chiral stacking outcomes, CSIs, are not mirror-imaged. With the increase of the molecular number in living units, the energy difference between CSIs can be amplified by self-replication of LSP, leading to handedness preference. Thus, the detectable CSA is mainly derived from the CSI with energetically favored hierarchical structure. Thus, our strategy breaks the stereotype that the complex molecular structure and symmetry breaking mechanism are necessary for the formation of detectable CSA by achiral molecules.

Background: Ischemic stroke (IS) is a serious neurological disease that largely results in long-term disability and death. Extensive evidence has indicated that the activation of inflammation and ferroptosis significantly contribute to the development of IS pathology. However, the underlying molecular mechanism remains unclear. In this study, we aimed to identify potential biomarkers associated with IS through the construction of a competing endogenous RNA (ceRNA) network and to investigate the possible inflammatory and ferroptosis-related molecular mechanisms., Results: We identified 178 differentially expressed target messenger RNAs (DETmRNAs) associated with IS. As revealed through enrichment analysis, the DEmRNAs were mainly enriched in the inflammatory signaling pathways and also related to ferroptosis mechanism. The CIBERSORT algorithm showed immune infiltration landscapes in which the naïve B cells, naïve T cells, and monocytes had statistically different numbers in the cerebral infarction group compared with the control group. A ceRNA network was constructed in this study involving 44 long non-coding RNAs (lncRNAs), 15 microRNAs (miRNAs), and 160 messenger RNAs (mRNAs). We used the receiver operating characteristic (ROC) analysis to identify three miRNAs (miR-103a-3p, miR-140-3p, and miR-17-5p), one mRNA (TLR4), and one lncRNA (NEAT1) as the potential key biomarkers of the ceRNA network. The key mRNA and lncRNA were shown to be highly related to the ferroptosis mechanism of IS. The expression of these key biomarkers was also further validated by a method of quantitative real-time polymerase chain reaction in SH-SY5Y cells, and the validated results were consistent with the findings predicted by bioinformatics., Conclusion: Our results suggest that the ceRNA network may exert an important role in the inflammatory and ferroptosis molecular mechanisms of IS, providing new insight into therapeutic IS targets., (© 2023. The Author(s).)

Objective: A combination of lateral soft tissue release, medial soft tissue contraction, vastus medialis anterior placement, medial patellofemoral ligament reconstruction, and rectus femoris insertion reconstruction are introduced in the treatment of habitual patellar dislocation in adolescents., Methods: A retrospective analysis was performed on 12 patients (17 knees) with habitual patellar dislocation and unclosed epiphyses who underwent surgical treatment at the First Hospital of Jilin University from May 2017 to November 2021. The Lysholm scores and Q angle were collected preoperatively and at final follow-up and were compared., Results: Twelve patients (4 boys and 8 girls) aged 10-15 years were retrospectively analysed, who followed up for an average of 21 months (5-48 months). The range of motion of the knee joint returned to normal in all patients, and no cases of complications including surgical site infection, joint stiffness, or patellar re-dislocation occurred. The mean Lysholm scores and Q angles improved from 73.9, and 19.6° preoperatively to 91.7, and 13.9° at the final follow-up, respectively., Conclusion: The preliminary effect of the combination surgery for habitual patellar dislocation in adolescents was satisfactory., (© 2023. The Author(s).)

Total knee arthroplasty (TKA) is widely used in clinical practice as an effective treatment for end-stage knee joint lesions. It can effectively correct joint deformities, relieve painful symptoms, and improve joint function. The reconstruction of lower extremity joint lines and soft tissue balance are important factors related to the durability of the implant; therefore, it is especially important to measure the joint lines and associated angles before TKA. In this article, we review the technological progress in the preoperative measurement of TKA.

Background: In recent years, non-invasive brain stimulation (NIBS) has been used for motor function recovery. However, the effects of NIBS in populations with spinal cord injury (SCI) remain unclear. This study aims to conduct a meta-analysis of the existing evidence on the effects and safety of NIBS against sham groups for motor dysfunction after SCI to provide a reference for clinical decision-making., Methods: Two investigators systematically screened English articles from PubMed, MEDLINE, Embase, and Cochrane Library for prospective randomized controlled trials regarding the effects of NIBS in motor function recovery after SCI. Studies with at least three sessions of NIBS were included. We assessed the methodological quality of the selected studies using the evidence-based Cochrane Collaboration's tool. A meta-analysis was performed by pooling the standardized mean difference (SMD) with 95% confidence intervals (CI)., Results: A total of 14 randomized control trials involving 225 participants were included. Nine studies used repetitive transcranial magnetic stimulation (rTMS) and five studies used transcranial direct current stimulation (tDCS). The meta-analysis showed that NIBS could improve the lower extremity strength (SMD = 0.58, 95% CI = 0.02-1.14, P = 0.004), balance (SMD = 0.64, 95% CI = 0.05-1.24, P = 0.03), and decrease the spasticity (SMD = - 0.64, 95% CI = - 1.20 to - 0.03, P = 0.04). However, the motor ability of the upper extremity in the NIBS groups was not statistically significant compared with those in the control groups (upper-extremity strength: P = 0.97; function: P = 0.56; and spasticity: P = 0.12). The functional mobility in the NIBS groups did not reach statistical significance when compared with the sham NIBS groups (sham groups). Only one patient reported seizures that occurred during stimulation, and no other types of serious adverse events were reported., Conclusion: NIBS appears to positively affect the motor function of the lower extremities in SCI patients, despite the marginal P-value and the high heterogeneity. Further high-quality clinical trials are needed to support or refute the use and optimize the stimulation parameters of NIBS in clinical practice., (© 2023. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the most frequent types of liver disease in pediatric populations with obesity. Tilianin has multiple biological activities including anti-inflammatory and antioxidant. Here, we aim to explore the functions and possible mechanisms of tilianin on NAFLD in obese children. A high-fat high-carbohydrate (HFHC) diet was used to feed 21-d-old mice. Tilianin was administered at a dose of 10 or 20 mg/kg daily. HFHC-fed mice gained weight, increased liver index. The liver showed hepatocyte ballooning, inflammatory infiltration, and steatosis. Elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) and reduced the high-density lipoprotein cholesterol (HDL-C) level were found in HFHC-fed mice. Administration of tilianin significantly reduced these impairments. We further evaluated proteins related to lipid metabolism and observed that LXRα, SREBP-1c, FAS and ACC1 expression were blunted following tilianin administration. In addition, tilianin suppressed reactive oxygen species (ROS) overproduction and lipid peroxide 4-Hydroxynonenal expression, ascribed to its oxidative stress-modulating capacity. Tilianin also reversed the increase in F4/80 expression and proinflammatory cytokine levels. Of note, tilianin administration resulted in decreased protein levels of active caspase-1 and NOD-like receptor protein 3 (NLRP3) in HFHC-fed mice. Our study suggests that tilianin may ameliorate NAFLD in early obese mice by modulating lipids metabolism, oxidative stress, and inflammation, which may in part involve inhibiting NLRP3 inflammasome activation.

Bacterial resistance is a growing threat to public health and a significant barrier to anti-infective treatment. Consequently, the development of novel antibacterial strategies to address this issue is critical. Herein, we developed a series of chalcone-alkyl-lysine compounds by mimicking the chemical structure and antibacterial properties of cationic antimicrobial peptides. Most of the compounds showed significant antibacterial activity against Gram-positive and Gram-negative bacteria. Compound 6d displayed potent antibacterial activity against Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), with MICs of 1-4 μg/mL. In addition, 6d exhibited excellent antibacterial activity against clinical MRSA and NDM-positive isolates, bactericidal properties, low resistance frequency. The mechanism studies revealed that compound 6d destroys bacterial cell membranes by interacting with phosphatidylglycerol (PG), causing the production of reactive oxygen species (ROS) and the leakage of nucleic acids, resulting in bacterial death. Furthermore, compound 6d did not exhibit any observable toxicity in HeLa and HEK293 cells at 8 × MIC. As a result, the findings suggest that compound 6d has potential therapeutic effects against bacterial infections and could be a promising drug candidate for future research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the difference of programmed death-ligand 1 (PD-L1) expression between primary lesions and lymph node metastatic lesions in oral squamous cell carcinoma. Methods: Eighty-two patients diagnosed with oral squamous cell carcinoma from December 2020 to July 2021 in Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine & College of Stomatology, Shanghai Jiao Tong University, were enrolled in this study. All the patients underwent neck dissection concurrently and had lymph node metastasis. Among them, there were 28 females and 54 males. The age range was 24-79 years old [(58.6±11.7) years old]. The expression of PD-L1 protein in primary tumors and lymph node metastatic lesions was detected by immunohistochemistry. Combined positive score (CPS) was used to evaluate the PD-L1 expression. And the difference of PD-L1 expression between primary tumors and metastatic lesions was analyzed. Results: Among 82 primary tumors, 9 cases (11%) had PD-L1 CPS<1, 31 cases (38%)≥ 1 and <20, and 42 cases (51%)≥20. Cases with perineural invasion had lower CPS (χ 2 =6.35, P =0.042). Among 82 matched lymph node metastatic lesions, 9 cases (11%) had CPS<1, 38 cases (46%)≥1 and<20, and 35 cases (43%)≥20. The CPS of 27 pairs (33%) of primary and metastatic lesions were discordant. The statistical results showed that the Kappa value of consistency evaluation was 0.446, indicating that the consistency of PD-L1 CPS in primary and metastatic lesions of OSCC was medium. Conclusions: There are differences in PD-L1 expression between the primary lesion of OSCC and cervical lymph node metastatic lesions, and the consistency is medium. In the routine practice, lymph node metastatic lesions should be carefully used to replace the primary lesion for PD-L1 CPS evaluating.

This study was designed to evaluate the bioequivalence of the newly developed delayed-release oral suspension (test) 40 mg esomeprazole magnesium compared to its marketed counterpart (40 mg; reference) in healthy adult Chinese subjects. We conducted randomized, open-label, two-period, single-dose, two-way crossover trials over a 7-day washout period, comprising a fasting trial and a fed trial. The subjects were administered the test or reference products in a 1:1 ratio at random throughout each period. Then, in the next session, they received the alternate products. Liquid chromatography-tandem mass spectrometry and WinNonlin software were used to assess the bioequivalence of esomeprazole peak plasma concentration (C max ) and area under the concentration-time curve (AUC). Overall, 33 subjects participated in the fasting trial and 42 subjects participated in the fed trial. Under both situations, the 90% confidence interval for the ratio of geometric means of C max , AUC 0-t , and AUC 0-∞ were within equivalence ranges (80%-125%). In these trials, no severe adverse events or protocol violations were observed. Moreover, when esomeprazole was administered while fed, the t max was delayed, and both C max and AUC were reduced. The results of this research suggest that the test and reference formulations were bioequivalent under fasting and fed states., (© 2022, The American College of Clinical Pharmacology.)

The present study compares the pharmacokinetics of amoxicillin and clavulanate potassium suspension (200 mg/28.5 mg) during fasting and postprandial conditions, and the sample adds a stabilizer study. Two randomized, crossover trials were conducted in an open-label, single-center study (a fasting trial and a postprandial trial). In each part of the study, the subjects were randomly assigned to receive either test or reference products (200 mg/28.5 mg) in a 1:1:1 ratio, followed by the alternative products after a 7-day washout period. Plasma amoxicillin and clavulanic acid concentrations were analyzed by liquid chromatography-tandem mass spectrometry. WinNonlin software was used to evaluate the pharmacokinetic parameters (noncompartmental model). The formulations were considered bioequivalent if the geometric means of area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C max ) of amoxicillin and clavulanic acid were within the predetermined bioequivalence range established by average bioequivalence (ABE) or reference-scaled ABE. Tolerability was assessed throughout the study. The postprandial trial and the fasting study each had 12 volunteers. Under fasting and postprandial conditions, the 90%CI for the ratio of geometric means of amoxicillin of C max , AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity were within the ABE acceptance limits (80%-125%); the geometric means of clavulanic acid of C max (critbound, -0.03; point estimate, 1.07) were within the reference-scaled ABE acceptance limits, and the AUC from time 0 to the last measurable concentration and AUC from time 0 to infinity were within the ABE acceptance limits (80%-125%). Time to maximum concentration of amoxicillin was delayed 1.0 hour with high-fat meals compared to fasting conditions. Meantime, high-fat meals decreased the exposure of clavulanic acid by nearly 40%. No serious adverse events were found among the subjects. The bioequivalence of test and reference amoxicillin and clavulanate potassium for suspension was validated in this study under fasting and postprandial conditions., (© 2022, The American College of Clinical Pharmacology.)

Background: To explore the rules of TCM medication in the treatment of constipation in network pharmacology., Methods: Collect and screen the clinical intervention literature on TCM for constipation from China's national knowledge infrastructure, Wanfang and VIP databases established a database of TCM for constipation, applied R software (3.3.1) to analyze the pattern of prescriptions for TCM for constipation, and summarized the core prescription. The effective active compounds and action targets in the core prescription were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Integrated Databases (TCMID), constipation-related targets were derived from the DisGeNET and GeneCards databases, Protein-protein interaction network (PPI) was drawn by STRING database, and enrichment analysis was conducted by the Clusterprofiler package in R software (3.3.1). Finally, molecular docking was used to validate the binding ability of candidate compounds to potential targets., Results: Two hundred sixteen target prescriptions were screened through data mining, involving 226 herbs. Association rule analysis results suggested that the "Angelicae sinensis-Radix-dried rehmanniae-Cistanche deserticola-Atractylodes macrocephala-Astragali Radix" was a strong affinity for medicine. Network pharmacology analysis of the core prescription resulted in the screening of 115 candidate compounds, such as quercetin, kaempferol, mangostin, eugenol A, and beta-sitosterol; 131 potential targets, such as PTGS2, PTGS1, and CHRM3; and 160 signaling pathways, such as lipid and atherosclerosis, proteoglycans in cancer, hepatitis B, Kaposi's sarcoma-associated herpesvirus infection, and PI3K/AKT pathways. Molecular docking showed that PTGS1-formononetin, PTGS2-kaempferol, and CHRM3-kaempferol were all well bound and well matched., Conclusions: This study provides a new method and ideas for clinical applications of integrated Chinese and western medicine in treating constipation., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Shu-Min Xu et al.)

Electrochemical reduction of biomass-derived 5-hydroxymethylfurfural (HMF) represents an elegant route toward sustainable value-added chemicals production that circumvents the use of fossil fuel and hydrogen. However, the reaction efficiency is hampered by the high voltage and low activity of electrodes (Cu, Bi, Pb). Herein, we report a Ru 1 Cu single-atom alloy (SAA) catalyst with isolated Ru atoms on Cu nanowires that exhibits an electrochemical reduction of HMF to 2,5-dihydroxymethylfuran (DHMF) with promoted productivity (0.47 vs. 0.08 mmol cm -2  h -1 ) and faradic efficiency (FE) (85.6 vs. 71.3 %) at -0.3 V (vs. RHE) compared with Cu counterpart. More importantly, the FE (87.5 %) is largely retained at high HMF concentration (100 mM). Kinetic studies by using combined electrochemical techniques suggest disparate mechanisms over Ru 1 Cu and Cu, revealing that single-atom Ru promotes the dissociation of water to produce H* species that effectively react with HMF via an electrocatalytic hydrogenation (ECH) mechanism., (© 2022 Wiley-VCH GmbH.)

Objectives: To determine the clinicopathological features of epithelioid sarcoma presenting in head and neck region (HNES) and elucidate diagnostic key points and treatment options for HNES., Materials and Methods: A total of 12 HNES cases were collected in our department from 2010 to 2020. Their clinical information and pathological features were documented, and relevant follow-up was performed. Immunohistochemistry was carried to analyze the protein markers of HNES., Results: Of the 12 HNES cases, 10 were primary tumors and 2 were metastasized from foot and shoulder, respectively. The patients with primary tumors were significantly younger than those with metastasized ones (22.7 vs 41.5, p = .0157), and male patients outnumbered female patients (3:1). Of all HNES cases, 9 were classic subtype, and 3 were proximal subtype. HNES patients had a poor prognosis, with 5-year overall survival of 41.5% and 5-year relapse-free survival of 22.5%. A loss of INI1 was identified as the hallmark of HNES with 83.3% (10/12) of HNES cases presenting as EZH2 positive., Conclusions: HNES is more prevalent at younger ages and in males, has a poor prognosis, and exhibits a greater proportion of classic subtype than proximal subtype. EZH2 inhibitor has therapeutic potential in HNES., (© 2021 Wiley Periodicals LLC.)

This study evaluated and compared the efficacy, safety and economy of four Chinese patent medicines(CPMs) in the treatment of functional dyspepsia(FD) using the method of rapid health technology assessment. It aims to provide decision-makers with rapid decision-making information. The eight Chinese and English databases were comprehensively and systematically searched for the relevant clinical research. Studies were screened and evaluated. A total of 110 studies were identified, including 95 randomized controlled trials(RCTs), 7 controlled clinical trials(CCTs), 7 systematic review/Meta-analysis and 1 economic evaluation, among which 28 were Dalitong Granules, 49 were Zhizhu Kuanzhong Capsules, 3 were Biling Weitong Granules and 30 were Qizhi Weitong Granules(Tablets/Capsules). The quality of the included literature was generally low. The efficacy of four CPMs alone or combined with western medicine in the treatment of FD is different. Dalitong Granules was used to treat motility disorder in FD. Zhizhu Kuanzhong Capsules and Qizhi Weitong Granules(Tablets/Capsules) can treat FD patients with anxiety and depression. Qizhi Weitong Granules(Tablets/Capsules) were mainly used in FD for perimenopausal patients. There were no serious adverse reactions in the clinical study of four CPMs in the treatment of FD. Dalitong Granules has better effects than mosapride in the treatment of FD, but the cost is slightly higher. The cost-effectiveness ratio of Zhizhu Kuanzhong Capsules in the treatment of FD patients with anxiety and depression was lower than that of Domperidone. In terms of average daily price, Qizhi Weitong Tablets has the highest price(27.00 yuan per day), Qizhi Weitong Granules has the lowest price(5.04 yuan per day), Biling Weitong Granules has a relatively high price(15.53 yuan per day), followed by Dalitong Granules(13.03 yuan per day). The evidence of Dalitong Granules covered the efficacy, safety and economy, which is relatively complete compared with the other three drugs. It has effective potential in the treatment of motility disorder in FD. Further research in this field in the future is needed.