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Patterns on polymers usually have different mechanical properties as those of the substrates, causing deformation or distortion and even detachment of the patterns from the polymer substrates. Herein, we present a wrinkling strategy, which utilizes photolithography to define the area of stress distribution by light-induced physical crosslinking of polymers and controls diffusion of residual solvent to redistribute the stress and then offers the same material for patterns as substrate by thermal polymerization, providing uniform wrinkles without worrying about force relaxation. The strategy allows the recording and hiding of up to eight switchable images in one place that can be read by the naked eye without crosstalk, applying the wrinkled polymer for optical anti-counterfeiting. The wrinkled polyimide film was also utilized to act as a substrate for the creation of fine copper circuit by a full-additive process. It generates flexible integrated circuit (IC) carrier board with copper wire density of 400% higher than that of the state-of-the-art in industry while fulfilling the standards for industrialization. Current wrinkling processes for pattern formation cannot be easily controlled, resulting in deformation or detachment of patterns from substrates. Here, Zhong et al. report a wrinkling strategy for creating patterned structures with long-range order and resistant to force relaxation. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease marked by inflammatory cell infiltration and joint damage. The Chinese government has approved the prescription medication sinomenine (SIN), an effective anti-inflammation drug, for treating RA. This study evaluated the possible anti-inflammatory actions of SIN in RA based on bioinformatics analysis and experiments. Six microarray datasets were acquired from the gene expression omnibus (GEO) database. We used R software to identify differentially expressed genes (DEGs) and perform function evaluations. The CIBERSORT was used to calculate the abundance of 22 infiltrating immune cells. The weighted gene co-expression network analysis (WGCNA) was used to discover genes associated with M1 macrophages. Four public datasets were used to predict the genes of SIN. Following that, function enrichment analysis for hub genes was performed. The cytoHubba and least absolute shrinkage and selection operator (LASSO) were employed to select hub genes, and their diagnostic effectiveness was predicted using the receiver operator characteristic (ROC) curve. Molecular docking was undertaken to confirm the affinity between the SIN and hub gene. Furthermore, the therapeutic efficacy of SIN was validated in LPS-induced RAW264.7 cells line using Western blot and Enzyme-linked immunosorbent assay (ELISA). The matrix metalloproteinase 9 (MMP9) was identified as the hub M1 macrophages-related biomarker in RA using bioinformatic analysis and molecular docking. Our study indicated that MMP9 took part in IL-17 and TNF signaling pathways. Furthermore, we found that SIN suppresses the MMP9 protein overexpression and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the LPS-induced RAW264.7 cell line. In conclusion, our work sheds new light on the pathophysiology of RA and identifies MMP9 as a possible RA key gene. In conclusion, the above findings demonstrate that SIN, from an emerging research perspective, might be a potential cost-effective anti-inflammatory medication for treating RA. [ABSTRACT FROM AUTHOR]

In this paper, an online energy-saving control allocation strategy based on self-updating loss estimation for multi-motor drive systems is proposed, where the impact of variations in motor parameters and distribution coefficients is considered. Firstly, a drive system model for multi-motor drive systems incorporating iron loss in permanent magnet synchronous motor (PMSM) is established. Then, a self-updating PMSM loss estimation method based on dynamic torque–current mapping is proposed. The torque–current mapping is initially identified based on the conv-fusion curve, and iteratively updated by optimal estimation. Subsequently, an online control allocation method based on line search is proposed, which mitigates the adverse effects caused by variations in distribution coefficients and reduces the total motor loss. Finally, the effectiveness of the proposed strategy is verified on the hardware-in-the-loop (HIL)-based platform. The results demonstrate that the strategy effectively enhances energy efficiency while maintaining the original control performance of the system. [ABSTRACT FROM AUTHOR]

Aims: The extent of perihematomal edema following intracerebral hemorrhage (ICH) significantly impacts patient prognosis, and disruption of the blood–brain barrier (BBB) exacerbates perihematomal edema. However, the role of peripheral IL‐10 in mitigating BBB disruption through pathways that link peripheral and central nervous system signals remains poorly understood. Methods: Recombinant IL‐10 was administered to ICH model mice via caudal vein injection, an IL‐10‐inhibiting adeno‐associated virus and an IL‐10 receptor knockout plasmid were delivered intraventricularly, and neurobehavioral deficits, perihematomal edema, BBB disruption, and the expression of JAK1 and STAT3 were evaluated. Results: Our study demonstrated that the peripheral cytokine IL‐10 mitigated BBB breakdown, perihematomal edema, and neurobehavioral deficits after ICH and that IL‐10 deficiency reversed these effects, likely through the IL‐10R/JAK1/STAT3 signaling pathway. Conclusions: Peripheral IL‐10 has the potential to reduce BBB damage and perihematomal edema following ICH and improve patient prognosis. [ABSTRACT FROM AUTHOR]

6-Hydroxydopamine (6-OHDA) is a classic neurotoxin that has been widely used in Parkinson's disease research. 6-OHDA can increase intracellular reactive oxygen species (ROS) and can cause cell damage, which can be attenuated with (-)-Epigallocatechin-3-gallate (EGCG) treatment. However, the mechanism by which EGCG alters the 6-OHDA toxicity remains unclear; In this study, we found 6-OHDA (25 μM) alone increased intracellular ROS concentration in N27 cells, which was attenuated by pretreating with EGCG (100 μM). We evaluated the intracellular oxidative damage by determining the level of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content. 6-OHDA significantly increased TBARS by 82.7% (P <.05) and protein carbonyl content by 47.8 (P <.05), compared to the control. Pretreatment of EGCG decreased TBARS and protein carbonyls by 36.4% (P <.001) and 27.7% (P <.05), respectively, compared to 6-OHDA alone treatment. Antioxidant effect was tested with E2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and peroxisome-proliferator activator receptor γ (PPARγ) expression. 6-OHDA increased Nrf2 expression by 69.6% (P <.001), HO-1 by 173.3% (P <.001), and PPARγ by 122.7% (P <.001), compared with untreatment. EGCG pretreatment stabilized these alterations induced by 6-OHDA. Our results suggested that the neurotoxicity of 6-OHDA in N27 cells was associated with ROS pathway, whereas pretreatment of EGCG suppressed the ROS generation and deactivated the Nrf2/HO-1 and PPARγ expression. [ABSTRACT FROM AUTHOR]

Background: Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood–brain barrier dysfunction and vasogenic brain edema. However, there is a few days between blood‒brain barrier dysfunction and vasogenic brain edema. The present study sought to investigate whether this phenomenon is caused by endothelial injury induced by the acute astrocytic barrier, also known as the glial limitans. Methods: Bioinformatics analyses of human endothelial cells and astrocytes under hypoxia were performed based on the GEO database. Wild-type, EGLN3 and PKM2 conditional knock-in mice were used to confirm glial limitan formation after SAH. Then, the effect of endothelial EGLN3-PKM2 signaling on temporal and spatial changes in glial limitans was evaluated in both in vivo and in vitro models of SAH. Results: The data indicate that in the acute phase after SAH, astrocytes can form a temporary protective barrier, the glia limitans, around blood vessels that helps maintain barrier function and improve neurological prognosis. Molecular docking studies have shown that endothelial cells and astrocytes can promote glial limitans-based protection against early brain injury through EGLN3/PKM2 signaling and further activation of the PKC/ERK/MAPK signaling pathway in astrocytes after SAH. Conclusion: Improving the ability to maintain glial limitans may be a new therapeutic strategy for improving the prognosis of SAH patients. [ABSTRACT FROM AUTHOR]

Commutation failures in line commuted converter-based high voltage direct current (LCC-HVDC) transmission systems leads to an increase in the converter bus voltage of the rectifier station, thus resulting in AC transient overvoltage in the sending-end grid. The transient overvoltage could lead to the disconnection of renewable energy generation and threaten the stable operation of the sending-end grid. However, the influences of the coupling between AC and DC systems caused by the interaction between the active and reactive power of the sending-end grid, the AC bus voltage of the rectifier station, and the DC current are ignored. The AC transient overvoltage cannot be accurately suppressed. Therefore, in this study, the transient voltage characteristics of the rectifier station under a commutation failure of the inverter station are analyzed. The influence of LCC-HVDC control on the AC bus voltage of a rectifier station through the active and reactive power of the rectifier station is analyzed. A dynamic model of the AC bus voltage of a rectifier station under an AC-DC system coupling is established. The calculation method of the command value of the DC current of the rectifier station is proposed by a predictive control model, and an improved suppression method for AC transient overvoltage is proposed. The case studies show that the accuracy and effectiveness of the suppression of AC transient overvoltage are improved by considering the coupling between AC and DC systems. [ABSTRACT FROM AUTHOR]

Background: The prevalence of depression among people with chronic pain remains unclear due to the heterogeneity of study samples and definitions of depression. We aimed to identify sources of variation in the prevalence of depression among people with chronic pain and generate clinical prediction models to estimate the probability of depression among individuals with chronic pain. Methods: Participants were from the UK Biobank. The primary outcome was a "lifetime" history of depression. The model's performance was evaluated using discrimination (optimism-corrected C statistic) and calibration (calibration plot). Results: Analyses included 24,405 patients with chronic pain (mean age 64.1 years). Among participants with chronic widespread pain, the prevalence of having a "lifetime" history of depression was 45.7% and varied (25.0–66.7%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.66; good calibration on the calibration plot) included age, BMI, smoking status, physical activity, socioeconomic status, gender, history of asthma, history of heart failure, and history of peripheral artery disease. Among participants with chronic regional pain, the prevalence of having a "lifetime" history of depression was 30.2% and varied (21.4–70.6%) depending on patient characteristics. The final clinical prediction model (optimism-corrected C statistic: 0.65; good calibration on the calibration plot) included age, gender, nature of pain, smoking status, regular opioid use, history of asthma, pain location that bothers you most, and BMI. Conclusions: There was substantial variability in the prevalence of depression among patients with chronic pain. Clinically relevant factors were selected to develop prediction models. Clinicians can use these models to assess patients' treatment needs. These predictors are convenient to collect during daily practice, making it easy for busy clinicians to use them. [ABSTRACT FROM AUTHOR]

Growth hormone inducible transmembrane protein (GHITM), one member of Bax inhibitory protein‐like family, has been rarely studied, and the clinical importance and biological functions of GHITM in kidney renal clear cell carcinoma (KIRC) still remain unknown. In the present study, we found that GHITM was downregulated in KIRC. Aberrant GHITM downregulation related to clinicopathological feature and unfavourable prognosis of KIRC patients. GHITM overexpression inhibited KIRC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, GHITM overexpression could induce the downregulation of Notch1, which acts as an oncogene in KIRC. Overexpression of Notch1 effectively rescued the inhibitory effect induced by GHITM upregulation. More importantly, GHITM could regulate PD‐L1 protein abundance and ectopic overexpression of GHITM enhanced the antitumour efficiency of PD‐1 blockade in KIRC, which provided new insights into antitumour therapy. Furthermore, we also showed that YY1 could decrease GHITM level via binding to its promoter. Taken together, our study revealed that GHITM was a promising therapeutic target for KIRC, which could modulate malignant phenotype and sensitivity to PD‐1 blockade of renal cancer cells via Notch signalling pathway. [ABSTRACT FROM AUTHOR]

The exploration of post-Lithium (Li) metals, such as Sodium (Na), Potassium (K), Magnesium (Mg), Calcium (Ca), Aluminum (Al), and Zinc (Zn), for electrochemical energy storage has been driven by the limited availability of Li and the higher theoretical specific energies compared to the state-of-the-art Li-ion batteries. Post-Li metal||S batteries have emerged as a promising system for practical applications. Yet, the insufficient understanding of quantitative cell parameters and the mechanisms of sulfur electrocatalytic conversion hinder the advancement of these battery technologies. This perspective offers a comprehensive analysis of electrode parameters, including S mass loading, S content, electrolyte/S ratio, and negative/positive electrode capacity ratio, in establishing the specific energy (Wh kg−1) of post-Li metal||S batteries. Additionally, we critically evaluate the progress in investigating electrochemical sulfur conversion via homogeneous and heterogeneous electrocatalytic approaches in both non-aqueous Na/K/Mg/Ca/Al||S and aqueous Zn||S batteries. Lastly, we provide a critical outlook on potential research directions for designing practical post-Li metal||S batteries.Post-lithium metal||S batteries show promise for practical applications, but limited understanding of cell parameters and sulfur electrocatalytic conversion hampers progress. This Perspective provides critical insights on potential research directions for designing practical post-lithium metal||S batteries. [ABSTRACT FROM AUTHOR]

Aims: Understanding the neural mechanisms underlying stroke recovery is critical to determine effective interventions for stroke rehabilitation. This study aims to systematically explore how recovery mechanisms post‐stroke differ between individuals with different levels of functional integrity of the ipsilesional corticomotor pathway and motor function. Methods: Eighty‐one stroke survivors and 15 age‐matched healthy adults participated in this study. We used transcranial magnetic stimulation (TMS), electroencephalography (EEG), and concurrent TMS‐EEG to investigate longitudinal neurophysiological changes post‐stroke, and their relationship with behavioral changes. Subgroup analysis was performed based on the presence of paretic motor evoked potentials and motor function. Results: Functional connectivity was increased dramatically in low‐functioning individuals without elicitable motor evoked potentials (MEPs), which showed a positive effect on motor recovery. Functional connectivity was increased gradually in higher‐functioning individuals without elicitable MEP during stroke recovery and influence from the contralesional hemisphere played a key role in motor recovery. In individuals with elicitable MEPs, negative correlations between interhemispheric functional connectivity and motor function suggest that the influence from the contralesional hemisphere may be detrimental to motor recovery. Conclusion: Our results demonstrate prominent clinical implications for individualized stroke rehabilitation based on both functional integrity of the ipsilesional corticomotor pathway and motor function. [ABSTRACT FROM AUTHOR]

Remote sensing technology applications for water quality inversion in large rivers are common. However, their application to medium/small-sized water bodies within rural areas is limited due to the low spatial resolution of remote sensing images. In this work, a typical small rural river was selected, and high-resolution unmanned aerial vehicle (UAV) multispectral images and ground monitoring data of the river were obtained. Then, a comparative analysis of three univariate regression models and nine machine learning models (Ridge Regression (RR), Support Vector Regression (SVR), Grid Search Support Vector Regression (GS-SVR), Random Forest (RF), Grid Search Random Forest (GS-RF), eXtreme Gradient Boosting (XGBoost), Deep Neural Networks (DNN), Convolutional Neural Networks (CNN), and Catboost Regression (CBR)) for their accuracy in the prediction of turbidity (TUB), total nitrogen (TN), and total phosphorus (TP) was performed. TUB can be achieved by simple statistical regression models. The CBR model exhibited the best performance for the three index inversions on the test set evaluation metrics: R2 (0.90~0.92), RMSE (7.57 × 10−3~1.59 mg/L), MAE (0.01~1.30 mg/L), RPD (3.21~3.56), and NSE (0.84~0.92). The water pollution of the study area was closely related to its land-use pattern, excessive and irrational fertilizer application, and distribution of pollutant outlets. [ABSTRACT FROM AUTHOR]

Background: Major perioperative complications of stent‐assisted embolization treated for aneurysmal subarachnoid hemorrhage patients include the formation of thromboembolic events (TEs) and hemorrhagic events (HEs), for which antiplatelet protocols play a key role. Methods: We conducted a single‐center retrospective analysis to compare the differences between arteriovenous tirofiban administration with traditional oral dual antiplatelet therapy (DAPT). A total of 417 consecutive patients were enrolled. General clinical characteristics, as well as the perioperative ischemic and hemorrhagic events, were retracted in digital documents. Logistic regression was conducted to identify both risk and protective factors of perioperative TEs and HEs. Results: Perioperative TEs occurred in 21 patients, with an overall perioperative TEs rate of approximately 5.04%; among these patients, the incidence of perioperative TEs in the tirofiban group was less than that in the DAPT group. Additionally, 66 patients developed perioperative HEs, with an incidence of approximately 15.83%; among these patients, the incidence of perioperative HEs was less than that in the DAPT group. No significant differences were seen between the two groups in terms of the mRS score at the time of discharge. Conclusion: This study indicated that an improved perioperative antiplatelet drug tirofiban was an independent protective factor for perioperative TEs in stent‐assisted embolization of ruptured intracranial aneurysms, but it did not impart an elevated risk of perioperative HEs and had no significant effects on the near‐term prognosis of the patients. [ABSTRACT FROM AUTHOR]

Natural molecular chaperones utilize spatially ordered multiple molecular forces to effectively regulate protein folding. However, synthesis of such molecules is a big challenge. The concept of "aggregate science" provides insights to construct chemical entities (aggregates) beyond molecular levels to mimic both the structure and function of natural chaperone. Inspired by this concept, herein we fabricate a novel multi‐interaction (i.e., electrostatic and hydrophobic interaction) cooperative nanochaperone (multi‐co‐nChap) to regulating protein folding. This multi‐co‐nChap is fabricated by rationally introducing electrostatic interactions to the surface (corona) and confined hydrophobic microdomains (shell) of traditional single‐hydrophobic interaction nanochaperone. We demonstrate that the corona electrostatic attraction facilitates the diffusion of clients into the hydrophobic microdomains, while the shell electrostatic interaction balances the capture and release of clients. By finely synergizing corona electrostatic attraction with shell electrostatic repulsion and hydrophobic interaction, the optimized multi‐co‐nChap effectively facilitated de novo folding of nascent polypeptides. Moreover, the synergy between corona electrostatic attraction, shell electrostatic attraction and shell hydrophobic interaction significantly enhanced the capability of multi‐co‐nChap to protect native proteins from denaturation at harsh temperatures. This work provides important insights for understanding and design of nanochaperone, which is a kind of ordered aggregate with chaperone‐like activity that beyond the level of single molecule. [ABSTRACT FROM AUTHOR]

The length of internodes plays a crucial role in determining the height of the castor plant (Ricinus communis L.). However, the specific mechanisms underlying internode elongation, particularly in the main stem of the castor plant, remain uncertain. To further investigate this, we conducted a study focusing on the internode tissue of the dwarf castor variety 071113, comparing it with the control high-stalk Zhuansihao. Our study included a cytological observation, physiological measurement, transcriptome sequencing, and metabolic determination. Our integrated findings reveal that the dwarf variety 071113 undergoes an earlier lignification development in the main stem and has a more active lignin synthesis pathway during internode intermediate development. In addition, the dwarf variety exhibited lower levels of the plant hormone indole-3-acetic acid (IAA), which had an impact on the development process. Furthermore, we identified specific enzymes and regulators that were enriched in the pathways of the cell cycle, auxin signal transduction, and secondary cell wall synthesis. Using these findings, we developed a model that explained the intermediate secondary growth observed in castor internode elongation and enhanced our comprehension of the dwarfing mechanism of the 071113 variety. This research provides a theoretical groundwork for the future breeding of dwarf castor varieties. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. Methods: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. Main results: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). Conclusions: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays. [ABSTRACT FROM AUTHOR]

Accurate prediction of spatial variation in water quality in small microwaters remains a challenging task due to the complexity and inherent limitations of the optical properties of small microwaters. In this paper, based on unmanned aerial vehicles (UAV) multispectral images and a small amount of measured water quality data, the performance of seven intelligent algorithm-optimized SVR models in predicting the concentration of chlorophyll (Chla), total phosphorus (TP), ammonia nitrogen (NH3-N), and turbidity (TUB) in small and micro water bodies were compared and analyzed. The results show that the Gray Wolf optimized SVR model (GWO-SVR) has the highest comprehensive performance, with R2 of 0.915, 0.827, 0.838, and 0.800, respectively. In addition, even when dealing with limited training samples and different data in different periods, the GWO-SVR model also shows remarkable stability and portability. Finally, according to the forecast results, the influencing factors of water pollution were discussed. This method has practical significance in improving the intelligence level of small and micro water body monitoring. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to investigate the neurological complications associated with coronavirus disease 19 (COVID‐19) during the 2022 Omicron wave. Methods and analysis: The medical records of a cohort of people admitted to neurological wards of three participating tertiary centres in Sichuan from 12 December 2022 to 12 January 2023 were reviewed. Demographics and clinical data were obtained and analysed with an interest in COVID‐19‐related new‐onset or worse neurological symptoms. The current data were also compared in two centres with similar data from the same period 12 months earlier. Results: In all, 790 people were enrolled, of whom 436 were positive for COVID‐19. Ninety‐nine had new onset COVID‐related neurological problems, or their known neurological condition deteriorated during the wave. There was a significant difference in demographics from the findings amongst admissions 12 months earlier as there was an increase in the average age, the incidence of encephalitis and encephalopathy, and mortality rates. One hundred and one received COVID‐specific antivirals, intravenous glucocorticoids and intravenous immunoglobulin therapy. No differences were seen between these and those who did not use them. Conclusion: New‐onset neurological conditions, particularly encephalitis and encephalopathy, increased significantly during this period. Deterioration of existing neurological conditions, such as seizure exacerbation, was also observed. A large‐scale treatment trial of people with COVID‐19 infection presenting with neurological disorders is still needed. [ABSTRACT FROM AUTHOR]

The development of a green, safe, and accurate sample preparation method for the determination of trace metal elements in environmental samples is of great importance. Choline chloride-based deep eutectic solvents (DESs) were used to extract heavy metal elements from litterfall and the target analytes were measured using inductively coupled plasma optical emission spectrometry. Factors such as the type, ratio, dosage, and extraction time and temperature of the DESs were studied. A DES system based on choline chloride and maleic acid had the highest extraction efficiency of 98.5%, 88.4%, 90.2%, and 93.7% for Cd, Cu, Zn, and Fe. Under the optimized conditions, the limits of detection and limits of quantification were in the range of 0.04-0.70 and 0.13-2.30 mg kg -1 . The repeatability ( n = 3), estimated in terms of the relative standard deviation, ranged from 1.14% to 3.40%. The proposed method was validated for accuracy using GBW10087. Notably, the energy consumption of the newly developed method was only one-fifth that of a traditional acid digestion method. This work not only presents an environmentally friendly method for the determination of trace element concentrations in environmental samples but also deepens our understanding of DES systems., Competing Interests: 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., (This journal is © The Royal Society of Chemistry.)

MDS1 and EVI1 complex locus (MECOM), a transcription factor encoding several variants, has been implicated in progression of ovarian cancer. The function of regulatory regions in regulating MECOM expression in ovarian cancer is not fully understood. In this study, MECOM expression was evaluated in ovarian cancer cell lines treated with bromodomain and extraterminal (BET) inhibitor JQ-1. Oncogenic phenotypes were assayed using assays of CCK-8, colony formation, wound-healing and transwell. Oncogenic phenotypes were estimated in stable sgRNA-transfected OVCAR3 cell lines. Xenograft mouse model was assayed via subcutaneous injection of enhancer-deleted OVCAR3 cell lines. The results displayed that expression of MECOM is downregulated in cell lines treated with JQ-1. Data from published ChIP-sequencing (H3K27Ac) in 3 ovarian cancer cell lines displayed a potential enhancer around the first exon. mRNA and protein expression were downregulated in OVCAR3 cells after deletion of the MECOM enhancer. Similarly, oncogenic phenotypes both in cells and in the xenograft mouse model were significantly attenuated. This study demonstrates that JQ-1 can inhibit the expression of MECOM and tumorigenesis. Deletion of the enhancer activity of MECOM has an indispensable role in inhibiting ovarian cancer progress, which sheds light on a promising opportunity for ovarian cancer treatment through the application of this non-coding DNA deletion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n = 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n = 130); and paclitaxel with cisplatin (TP group; n = 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1-32.0, P < 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7-18.1, P = 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034 ., (© 2024. The Author(s).)

Post-stroke depression is a common complication that imposes significant burdens and challenges on patients. The occurrence of depression is often associated with frontal lobe hemorrhage, however, current understanding of the underlying mechanisms remains limited. Here, the pathogenic mechanisms associated with the circuitry connectivity, electrophysiological alterations, and molecular characteristics are investigated related to the frontal lobe in adult male mice following unilateral injection of blood in the medial prefrontal cortex (mPFC). It is demonstrated that depression is a specific neurological complication in the unilateral hematoma model of the mPFC, and the ventral tegmental area (VTA) shows a higher percentage of connectivity disruption compared to the lateral habenula (LHb) and striatum (STR). Additionally, long-range projections originating from the frontal lobe demonstrate higher damage percentages within the connections between each region and the mPFC. mPFC neurons reveal reduced neuronal excitability and altered synaptic communication. Furthermore, transcriptomic analysis identifies the involvement of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway, and targeting the JAK-STAT pathway significantly alleviates the severity of depressive symptoms. These findings improve the understanding of post-hemorrhagic depression and may guide the development of efficient treatments., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: This study aimed to describe the experience of a single institution in China in treating adenoid cystic carcinoma of the nasopharynx. Methods: We reviewed the previous literature and conducted a retrospective analysis of 12 patients who diagnosed with nasopharyngeal adenoid cystic carcinoma (NACC) in clinical data, treatment, and follow-up data during 2019 to 2021. Results: Patients ranged in age from 32 to 68 years (mean 40.7 years, median 48.5 years), with a male to female ratio of 5:7. Most of our patients have T4a and T4b diseases (50% and 25%, respectively). A quarter of patients develop distant metastases. Among the 12 patients, 7 of them have positive margins under the microscope (7/12, 58.3%). The chief clinical manifestations were epistaxis, facial swelling, facial pain, headache ear stuffy, and hearing loss. If the tumors involved with cavernous sinus, brain stem infiltrated, and internal carotid artery circumvented, patients will undertake routine enhanced magnetic resonance imaging with Magnetic Resonance Angiography/Magnetic Resonance Venogram (MRA/MRV) to clearly show the lesion region. All patients underwent endoscopic endonasal approach. Fifty percent of patients received radiotherapy and 25% of patients received chemotherapy. None of the patients was lost and the follow-up time ranged from 16 to 45 months. The mean and median follow-up were 2.08 and 1.58 years. Two patients were dead of distant metastasis within 18 and 20 months after the surgery, and another patient with recurrent NACC died of hemorrhage. Conclusion: NACC is a rare malignant tumor that occurs in the nasopharynx, which can grow along the nerve, destroy the bone of the skull base, and metastasize to other organs. Up to now, there is no standard treatment. Our results show that endoscopic sinus surgery is a better choice for advanced or recurrent NACC., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add-on ASMs for the treatment of focal epilepsy using network meta-analysis., Methods: Data through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment-emergent adverse events (TEAEs) and individual TEAEs were assessed. "Gemtc" 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI)., Results: Literature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00-5.70) and 100% for rufinamide (2.03; 95% CI: 0.54-11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56-323.9) and zonisamide (10.63; 95% CI: 1.37-261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7-0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94-1.1; SUCRA: 0.885067) for overall TEAE compared with other medications., Significance: All approved ASMs were effective as add-on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom., Plain Language Summary: This article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of the hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Zhang et al.)

Periodontal disease ranks third among noncommunicable illnesses, behind cancer and cardiovascular disease, and is closely related to the occurrence and progression of various systemic diseases. However, elucidating the processes of periodontal disease and promoting periodontal bone regeneration remains a challenge. Here, quercetin is demonstrated to reduce the oxidative stress state of orofacial mesenchymal stem cells (OMSCs) in vitro and to affect the osteogenic growth of OMSCs through molecular mechanisms that mediate the m6A change in Per1. Nevertheless, the limited therapeutic efficacy of systemic medication and the limitations of local medication resulting from the small, moist, and highly dynamic periodontal environment make it challenging to treat periodontal tissues with medication. Herein, a biosafe injectable hydrogel drug-controlled delivery system is constructed as a bone-enhancing factory and loaded with quercetin to treat oxidative stress injury in periodontal tissues. This drug-carrying system made up of nanoscale bioglass microspheres and a light-cured injectable hydrogel, allows effective drug particle loading and cementation in the dynamic and moist periodontal environment. Furthermore, the system demonstrates the ability to stimulate OMSCs osteogenic differentiation in a Per1-dependent manner, which ultimately promotes periodontal bone repair, suggesting that this system has potential for clinical periodontal therapy., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)