Search

Hui Ye,1,2 Jiansong Tong,2 Jianzhang Wu,3 Xia Xu,4 Shenjie Wu,5 Botao Tan,6 Mengjing Shi,5 Jianguang Wang,1 Weibo Zhao,5 Heng Jiang,5 Sha Jin5 1School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Cellular and Molecular Biology, Scripps Research Institute, La Jolla, CA, USA; 3Pharmaceutical College, Wenzhou Medical University, Wenzhou, 4School of Medicine, Zhejiang University, Hangzhou, 5School of the 1st Clinical Medical Sciences, Wenzhou Medical University, Wenzhou, 6School of Medicine, Lishui University, Lishui, People’s Republic of China Abstract: Magnetoliposomes are phospholipid vesicles encapsulating magnetic nanoparticles that can be used to encapsulate therapeutic drugs for delivery into specific organs. Herein, we developed magnetoliposomes containing recombinant human IFNα2b, designated as MIL, and evaluated this combination’s biological safety and therapeutic effect on both cellular and animal hepatocellular carcinoma models. Our data showed that MIL neither hemolyzed erythrocytes nor affected platelet-aggregation rates in blood. Nitroblue tetrazolium-reducing testing showed that MIL did not change the absolute numbers or phagocytic activities of leukocytes. Acute-toxicity testing also showed that MIL had no devastating effect on mice behaviors. All the results indicated that the nanoparticles could be a safe biomaterial. Pharmacokinetic analysis and tissue-distribution studies showed that MIL maintained stable and sustained drug concentrations in target organs under a magnetic field, helped to increase bioavailability, and reduced administration time. MIL also dramatically inhibited the growth of hepatoma cells. Targeting of MIL in the livers of nude mice bearing human hepatocellular carcinoma showed that MIL significantly reduced the tumor size to 38% of that of the control group. Further studies proved that growth inhibition of cells or tumors was due to apoptosis-signaling pathway activation by human IFNα2b. Keywords: recombinant human interferon-α2b, magnetoliposome, hepatocellular carcinoma

Parkinson's disease (PD) pathogenesis is characterized by α-synuclein (α-syn) pathology, which is influenced by various factors such as neuroinflammation and senescence. Increasing evidence has suggested a pivotal role for Interleukin-17A(IL-17A) and Interleukin-17 Receptor A (IL-17RA) in PD, yet the trigger and impact of IL-17A/IL-17RA activation in PD remains elusive. This study observed an age-related increase in IL-17A and IL-17RA in the human central nervous system, accompanied by increased α-syn and senescence biomarkers. Interestingly, both levels of IL-17A and IL-17RA in PD patients were significantly elevated compared to age-matched controls, wherein the IL-17A was mainly present in neurons. This abnormal neuronal IL-17A activation in the PD brain was recapitulated in α-syn mouse models. Correspondingly, administration of recombinant IL-17A exacerbated pathological α-syn in both neuron and mouse models. Furthermore, IL-17A/IL-17RA pathway interventions via blocking antibody or shRNA-mediated knockdown can mitigate the effects of pathological α-syn. This study reveals an interplay between dysregulation of the IL-17A/IL-17RA pathway and α-syn, suggesting that regulating the IL-17A/IL-17RA pathway could modify PD progression by disrupting the detrimental cycle., 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 © 2024. Published by Elsevier Inc.)

As a major contributor to neonatal death and neurological sequelae, hypoxic-ischemic encephalopathy (HIE) lacks a viable medication for treatment. Oxidative stress induced by hypoxic-ischemic brain damage (HIBD) predisposes neurons to ferroptosis due to the fact that neonates accumulate high levels of polyunsaturated fatty acids for their brain developmental needs but their antioxidant capacity is immature. Ferroptosis is a form of cell death caused by excessive accumulation of iron-dependent lipid peroxidation and is closely associated with mitochondria. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. In this study we employed mitophagy agonists and inhibitors to explore the mechanisms by which mitophagy exerted ferroptosis resistance in a neonatal rat HIE model. Seven-days-old neonatal rats were subjected to ligation of the right common carotid artery, followed by exposure to hypoxia for 2 h. The neonatal rats were treated with a mitophagy activator Tat-SPK2 peptide (0.5, 1 mg/kg, i.p.) 1 h before hypoxia, or in combination with mitochondrial division inhibitor-1 (Mdivi-1, 20 mg/kg, i.p.), and ferroptosis inhibitor Ferrostatin-1 (Fer-1) (2 mg/kg, i.p.) at the end of the hypoxia period. The regulation of ferroptosis by mitophagy was also investigated in primary cortical neurons or PC12 cells in vitro subjected to 4 or 6 h of OGD followed by 24 h of reperfusion. We showed that HIBD induced mitochondrial damage, ROS overproduction, intracellular iron accumulation, lipid peroxidation and ferroptosis, which were significantly reduced by the pretreatment with Tat-SPK2 peptide, and aggravated by the treatment with Mdivi-1 or BNIP3 knockdown. Ferroptosis inhibitors Fer-1 and deferoxamine B (DFO) reversed the accumulation of iron and lipid peroxides caused by Mdivi-1, hence reducing ferroptosis triggered by HI. We demonstrated that Tat-SPK2 peptide-activated BNIP3-mediated mitophagy did not alleviate neuronal ferroptosis through the GPX4-GSH pathway. BNIP3-mediated mitophagy drove the P62-KEAP1-NRF2 pathway, which conferred ferroptosis resistance by maintaining iron and redox homeostasis via the regulation of FTH1, HO-1, and DHODH/FSP1-CoQ10-NADH. This study may provide a new perspective and a therapeutic drug for the treatment of neonatal HIE., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Metabolic reprogramming occurs in cardiomyopathy and heart failure contributing to progression of the disease. Activation of cardiac Hippo pathway signaling has been implicated in mediating mitochondrial dysfunction and metabolic reprogramming in cardiomyopathy, albeit influence of Hippo pathway on lipid profile is unclear. Using a dual-omics approach, we determined alterations of cardiac lipids in a mouse model of cardiomyopathy due to enhanced Hippo signaling and explored molecular mechanisms. Lipidomic profiling discovered multiple alterations in lipid classes, notably reduction of triacylglycerol, diacylglycerol, phospholipids and ether lipids, and elevation of sphingolipids and lysophosphatidylcholine. Mechanistically, we found downregulated expression of PPARα and PGC-1α at mRNA and protein levels, and downregulated expression of PPARα-target genes, indicating attenuated transcriptional activity of PPARα/PGC-1α. Lipidomics-guided transcriptomic analysis revealed dysregulated expression of gene sets that were responsible for enhanced biosynthesis of ceramides, suppression of TG biosynthesis, storage, hydrolysis and mitochondrial fatty acid oxidation, and reduction of peroxisome-localized biosynthesis of ether lipids. Collectively, Hippo pathway activation with attenuated PPARα/PGC-1α signaling is the underlying mechanism for alterations in cardiac lipids in cardiomyopathy and failing heart., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest involved in this work., (Copyright © 2024. Published by Elsevier B.V.)

As industrial informatization progresses, virtual simulation technologies are increasingly demonstrating their potential in industrial applications. These systems utilize various sensors to capture real-time factory data, which are then transmitted to servers via communication interfaces to construct corresponding digital models. This integration facilitates tasks such as monitoring and prediction, enabling more accurate and convenient production scheduling and forecasting. This is particularly significant for flexible or mixed-flow production modes. Bionic optimization algorithms have demonstrated strong performance in factory scheduling and operations. Centered around these algorithms, researchers have explored various strategies to enhance efficiency and optimize processes within manufacturing environments.This study introduces an efficient migratory bird optimization algorithm designed to address production scheduling challenges in an assembly shop with mold quantity constraints. The research aims to minimize the maximum completion time in a batch flow mixed assembly flow shop scheduling problem, incorporating variable batch partitioning strategies. A tailored virtual simulation framework supports this objective. The algorithm employs a two-stage encoding mechanism for batch partitioning and sequencing, adapted to the unique constraints of each production stage. To enhance the search performance of the neighborhood structure, the study identifies and analyzes optimization strategies for batch partitioning and sequencing, and incorporates an adaptive neighborhood structure adjustment strategy. A competition mechanism is also designed to enhance the algorithm's optimization efficiency. Simulation experiments of varying scales demonstrate the effectiveness of the variable batch partitioning strategy, showing a 5-6% improvement over equal batch strategies. Results across different scales and parameters confirm the robustness of the algorithm.

Background: Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT)., Methods: From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model., Results: Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered a stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR., Conclusion: Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD., Methods: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler., Results: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed., Conclusions: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events., (© 2024. The Author(s).)

Physical unclonable functions (PUFs) have emerged as an unprecedented solution for modern information security and anticounterfeiting by virtue of their inherent unclonable nature derived from distinctive, randomly generated physical patterns that defy replication. However, the creation of traceable optical PUF tags remains a formidable challenge. Here, we demonstrate a traceable PUF system whose unclonability arises from the random distribution of diamonds and the random intensity of the narrow emission from germanium vacancies (GeV) within the diamonds. Tamper-resistant PUF labels can be manufactured on diverse and intricate structural surfaces by blending diamond particles into polydimethylsiloxane (PDMS) and strategically depositing them onto the surface of objects. The resulting PUF codes exhibit essentially perfect uniformity, uniqueness, reproducibility, and substantial encoding capacity, making them applicable as a private key to fulfill the customization demands of circulating commodities. Through integration of a digitized "challenge-response" protocol, a traceable and highly secure PUF system can be established, which is seamlessly compatible with contemporary digital information technology. Thus, the GeV-PUF system holds significant promise for applications in data security and blockchain anticounterfeiting, providing robust and adaptive solutions to address the dynamic demands of these domains.

Mitochondria and the endoplasmic reticulum (ER) are vital organelles that influence various cellular physiological and pathological processes. Recent evidence shows that about 5%-20% of the mitochondrial outer membrane is capable of forming a highly dynamic physical connection with the ER, maintained at a distance of 10-30 nm. These interconnections, known as MAMs, represent a relatively conserved structure in eukaryotic cells, acting as a critical platform for material exchange between mitochondria and the ER to maintain various aspects of cellular homeostasis. Particularly, ER-mediated Ca 2+ release and recycling are intricately associated with the structure and functionality of MAMs. Thus, MAMs are integral in intracellular Ca 2+ transport and the maintenance of Ca 2+ homeostasis, playing an essential role in various cellular activities including metabolic regulation, signal transduction, autophagy, and apoptosis. The disruption of MAMs observed in certain pathologies such as cardiovascular and neurodegenerative diseases as well as cancers leads to a disturbance in Ca 2+ homeostasis. This imbalance potentially aggravates pathological alterations and disease progression. Consequently, a thorough understanding of the link between MAM-mediated Ca 2+ transport and these diseases could unveil new perspectives and therapeutic strategies. This review focuses on the changes in MAMs function during disease progression and their implications in relation to MAM-associated Ca 2+ transport., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: This study aims to evaluate the long-term outcome and prognostic factors of a "mother-child" coaxial dual-catheter technique for percutaneous transluminal angioplasty (PTA) in the treatment of central vein stenosis (CVS) or central vein occlusion (CVO)., Materials and Methods: During September 2017 to August 2020, totally, 76 hemodialysis patients with symptomatic CVS or CVO were treated with PTA using the mother-child technique. The success rate, complications, and follow-up information were collected. Cox proportional hazard analysis was used to explore the predicting factors of primary patency. Primary patency rates of different subgroups were generated with the Kaplan-Meier analysis and compared using the log-rank (Mantel-Cox) test., Results: There were 31 CVS patients and 45 CVO patients who presented with 114 PTAs. The initial procedure success rate was 98.25%. By the end of the follow-up, 57 patients (75%) had maintained functioning fistula after initial or repeated PTAs. The primary patency rates were 88.75% at 3 months, 73.36% at 6 months, 55.83% at 12 months, and 50.75% at 18 months. The secondary patency rates were 97.14% at 6 months, 87.66% at 12 months, and 82.18% at 24 months. The predictors for primary patency were history diabetes mellitus (hazard ratio [HR] = 3.1, 95% confidence interval [CI]: 1.31-7.30, P = .010), abnormal white blood cell count (HR = 1.44, 95% CI: 1.18-1.75, P < .001), lesion at subclavian-innominate vein (HR=2.75, 95% CI: 1.34-5.63, P = .006), and occlusion (HR=0.33, 95% CI: 0.14-0.76, P = .010). The primary patency was significantly lower in the subclavian-innominate vein subgroup, with a median primary patency of 4.5 (3-12.75) months, than in the nonsubclavian-innominate vein subgroup (8.5 [5-13] months; P = .005). The median duration of each PTA was 8 months for the first PTA, 7.5 months for the second PTA, and 5 months for the third PTA. There was no significant difference in the patency duration of repeated PTAs and the primary PTA ( P = .389)., Conclusions: The mother-child coaxial dual-catheter technique has a good success rate and acceptable primary patency in the treatment of hemodialysis patients with CVS or CVO. Repeated PTA is as effective as the primary PTA., Clinical Impact: This is the follow up report on the "Mother-Child" coaxial dual-catheter technique for percutaneous transluminal angioplasty of central vein stenosis or occlusion in hemodialysis patients since we first presented it in 2019. In this paper, we can see that the long-term patency rate of this technique for central venous disease is satisfactory, and repeated use of this technique does not affect the patency time. Compared with other literature reports, the surgical success rate of this technique is significantly improved. Therefore, this technique is worth popularizing in the treatment of central venous disease., 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: To explore the operational accuracy and operative time of oral surgery robot-assisted endodontic microsurgery on a head-simulator for clinical reference. Methods: Three pairs of surgical simulation models were set up on head-simulator. Each model included 10 positions anteriorly and posteriorly, 20 teeth for each technique, for a total of 60 teeth. An attending physician with more than 3 years clinical experience in endodontic microsurgery completed fixed-point osteotomy and apicoectomy in three groups of endodontic microsurgery under freehand (FH), static navigation (SN), and surgery robot (SR). The duration of each operation was recorded. Cone-beam CT was taken before the operation and the surgical path was planned in the software; after surgery, a plug gauge (precision gauge for measuring hole dimensions) was inserted into the surgical path for intraoral scanning. Surgical accuracy (starting point, end point, and angular deviation) was assessed in all 3 groups, and surgery time was compared. Results: The deviation at the starting point and the end point, and angular deviation was (0.37±0.11), (0.37±0.10) mm, and 0.71°±0.17°in the SR group. The deviations in the SR group were significantly lower than those in the SN group [(0.59±0.14), (0.65±0.18) mm, and 2.64°±0.75°] (P<0.05), and both groups were significantly lower than the FH group [(1.37±0.31), (1.10±0.21) mm, and 9.84°±3.15°] (P<0.05). The operative time in the SN group [(1.20±0.03) min] was significantly less than that in the SR group [(2.18±0.03) min] (P<0.05), and both groups were significantly less than that in the FH group [(8.70±3.15) min] (P<0.05). Starting point deviation, end point deviation, and angular deviation [(1.09±0.10), (0.90±0.07) mm, 7.22°±1.13°] in anterior teeth using the FH was significantly lower than the starting deviation, endpoint deviation, and angular deviation [(1.65±0.14), (1.30±0.06) mm, 12.46°±2.10°] in the posterior teeth using FH (P<0.05), and the operative time in the anterior teeth using the FH [(5.75±0.57) min] was significantly less than that in the posterior teeth using [(11.65±1.14) min] (P<0.05). The difference in accuracy and operative time between using SN and SR on anterior and posterior teeth was not statistically significant (P>0.05). Conclusions: Oral surgery robot-assisted endodontic microsurgery helps improving the accuracy of clinicians' operations and shorten the operation time.

Purpose: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries., Methods: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1 , Q 3 ). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve., Results: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 - 25.42, p = 0.002), 2.85 (95% CI: 1.11 - 7.31, p = 0.030), 2.62 (95% CI: 1.12 - 6.13, p = 0.027), 2.44 (95% CI: 1.25 - 4.76, p = 0.009), and 1.5 (95% CI: 1.10 - 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2  = 13.82, adjusted R 2  = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2  = 18.48, adjusted R 2  = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively., Conclusion: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI., (Copyright © 2024 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Chimeric antigen receptor T (CAR-T) cell therapy is a promising and precise targeted therapy for cancer that has demonstrated notable potential in clinical applications. However, severe adverse effects limit the clinical application of this therapy and are mainly caused by uncontrollable activation of CAR-T cells, including excessive immune response activation due to unregulated CAR-T cell action time, as well as toxicity resulting from improper spatial localization. Therefore, to enhance controllability and safety, a control module for CAR-T cells is proposed. Synthetic biology based on genetic engineering techniques is being used to construct artificial cells or organisms for specific purposes. This approach has been explored in recent years as a means of achieving controllability in CAR-T cell therapy. In this review, we summarize the recent advances in synthetic biology methods used to address the major adverse effects of CAR-T cell therapy in both the temporal and spatial dimensions.

Long-lasting and highly efficient antibacterial fabrics play a key role in public health occurrences caused by bacterial and viral infections. However, the production of antibacterial fabrics with a large size, highly efficient, and broad-spectrum antibacterial performance remains a great challenge due to the complex processes. Herein, we demonstrate sizable and highly efficient antibacterial fabrics through hydrogen bonding interaction and electrostatic interaction between surface groups of ZnO nanoparticles and fabric fibers. The production process can be carried out at room temperature and achieve a production rate of 300 × 1 m 2 within 1 h. Under both visible light and dark conditions, the bactericidal rate against Gram-positive ( S. aureus ), Gram-negative ( E. coli ), and multidrug-resistant (MRSA) bacteria can reach an impressive 99.99%. Furthermore, the fabricated ZnO nanoparticle-decorated antibacterial fabrics (ZnO@fabric) show high stability and long-lasting antibacterial performance, making them easy to develop into variable antibacterial blocks for protection suits.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to investigate the serum interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) levels in patients with ankylosing spondylitis (AS), and the correlation between serum levels and disease activity., Patients and Methods: ELISA was used to detect the serum TNF-α and IL-6 levels of AS patients (n=40) and normal controls (n=40) who were hospitalized or outpatient-diagnosed from June 2021 to May 2023. C-reactive protein (CRP) was detected by immune-enhanced turbidimetry. The erythrocyte sedimentation rate was determined by Wei's manual method. The correlation was analyzed by Pearson's correlation analysis., Results: The levels of TNF-α and IL-6 in the AS group were significantly higher than those in the control group, and the levels of TNF-α and IL-6 in AS patients in the active phase were higher than those in the stable phase (p<0.05). CRP level was positively correlated with TNF-α, and IL-6 (r=0.02886 and 0.0273, p<0.05). Erythrocyte sedimentation rate (ESR) level was also positively correlated with TNF-α, and IL-6 (r=0.07568 and 0.0613, p<0.05)., Conclusions: Serum TNF-α and IL-6 levels are correlated with AS disease activity, suggesting that they may be involved in the inflammatory response of AS.

Background: Yujin powder (YJP) is a classic prescription for treating dampness-heat diarrhea (DHD) in Traditional Chinese Medicine (TCM), but the main functional active ingredients and the exact mechanisms have not been systematically studied., Objectives: This study aimed to preliminarily explore the potential mechanisms of YJP for treating DHD by integrating UPLC-MS/MS and network pharmacology methods., Methods: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the ingredients of YJP. And then, the targets of these components were predicted and screened from TCMSP, SwissTargetPrediction databases. The disease targets related to DHD were obtained by using the databases of GeneCards, OMIM, DisGeNET, TTD, and DrugBank. The protein-protein interaction networks (PPI) of YJP-DHD were constructed using the STRING database and Origin 2022 software to identify the cross-targets by screening the core-acting targets and a network diagram by Cytoscape 3.8.2 software was also constructed. Metascape database was used for performing GO and KEGG enrichment anlysis on the core genes. Finally, molecular docking was used to verify the results with AutoDock 4.2.6, AutoDock Tools 1.5.6, PyMOL 2.4.0, and Open Babel 2.3.2 software., Results: 597 components in YJP were detected, and 153 active components were obtained through database screening, among them the key active ingredients include coptisine, berberine, baicalein, etc. There were 362 targets treating DHD, among them the core targets included TNF, IL-6, ALB, etc. The enriched KEGG pathways mainly involve PI3K-Akt, TNF, MAPK, etc. Molecular docking results showed that coptisine, berberine, baicalein, etc., had a strong affinity with TNF, IL-6, and MAPK14. Therefore, TNF, IL-6, MAPK14, ALB, etc., are the key targets of the active ingredients of YJP coptisine, baicalein, and berberine, etc. They have the potential to regulate PI3K-Akt, MAPK, and TNF signalling pathways. The component-target-disease network diagram revealed that YJP treated DHD through the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury., Conclusion: It is demonstrated that YJP treats DHD mainly through the main active ingredients coptisine, berberine, baicalein, etc. comprehensively exerting the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury, which will provide evidence for further in-depth studying the mechanism of YJP treating DHD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The issues of fruit waste and safety resulting from rot have spurred a demand for improved packaging systems. Herein, we present highly antibacterial and antioxidative carbon nanodot/silk fibroin (CD/SF) films for fruit preservation. The films are composed of CDs and SF together with a small amount of glycerol via hydrogen bonding, exhibiting outstanding biosafety, transparency, and stretchability. The films effectively integrate key functionalities (atmosphere control, resistance to food-borne pathogens, and antioxidation properties) and can be manufactured in large sizes (about 20 × 30 cm), boasting a transmission rate of 13 183 cm 3 /m 2 ·day for oxygen and 2860 g/m 2 ·day for water vapor, favoring the preservation of fresh fruits. A convenient dip-coating method enables in situ fabrication of films with a thickness of approximately 14 μm directly on the fruits' surface providing comprehensive protection. Importantly, the films are washable and biodegradable. This work presents a promising technology to produce multifunctional and eco-friendly antibacterial packaging systems.

Background: Chemical fungicides are the mainstay of plant disease control in agricultural production, but there are a very limited number of drugs that can effectively control plant diseases. Two series of secondary amine derivatives were synthesized using the diamine skeleton combined with saturated aromatic and aliphatic aldehydes, and their antibacterial and antifungal activities against plant pathogens were determined. In addition, the antimicrobial mechanism of the highly active compound A26 was preliminarily examined against Xanthomonas oryzae (Xoo)., Results: Compound A26 exhibited the highest antibacterial potency among all the target compounds, with MIC values of 3.12, 3.12 and 12.5 μg mL -1 against Xoo, Xanthomonas axonopodis pv. Citri and Pseudomonas sollamacearum, respectively. In addition, compound A26 had powerful curative and protective effects against Xoo at 200 μg mL -1 , and was better than the control agent Xinjunan. Preliminary mechanistic studies showed that compound A26 reduced the bacterial pathogenicity by targeting cell membranes and inhibiting the secretion of extracellular polysaccharides. Meanwhile, the toxicity of compound A26 to Human Embryonic Kidney 293 cells and Human Liver-7702 was similar to that of Xinjunan, and it had moderate toxicity according to the World Health Organization classification standard of oral exogenous toxicity, with an LD 50 of 245.47 mg kg -1 ., Conclusion: Secondary amines have efficient and broad-spectrum antibacterial activity against plant pathogenic bacteria and are expected to be a new class of candidate compounds for antibacterial drugs. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Aspergillus flavus, a widespread saprotrophic filamentous fungus, could colonize agricultural crops with aflatoxin contamination, which endangers food security and the agricultural economy. A safe, effective and environmentally friendly fungicide is urgently needed. Pterostilbene, a natural phytoalexin originated from Pterocarpus indicus Willd., Vaccinium spp. and Vitis vinifera L., has been reported to possess excellent antimicrobial activity. More importantly, it is quite safe and healthy. In our screening tests of plant polyphenols for the inhibition of A. flavus, we found that pterostilbene evidently inhibited mycelial growth of Aspergillus flavus (EC 50  = 15.94 μg/mL) and the inhibitory effect was better than that of natamycin (EC 50  = 22.01 μg/mL), which is a natural product widely used in food preservation. Therefore, we provided insights into the efficacy of pterostilbene suppression on A. flavus growth, aflatoxin B 1 biosynthesis and its potential mechanisms against A. flavus in the present study. Here, pterostilbene at concentrations of 250 and 500 μg/mL could effectively inhibit the infection of A. flavus on peanuts. And the biosynthesis of the secondary metabolite aflatoxin B 1 was also inhibited. The antifungal effects of pterostilbene are exerted by inducing a large amount of intracellular reactive oxygen species production to bring the cells into a state of oxidative stress, damaging cellular biomolecules such as DNA, proteins and lipids and destroying the integrity of the cell membrane. Taken together, our study strongly supported the fact that pterostilbene could be considered a safe and effective antifungal agent against A. flavus infection., Competing Interests: Declaration of competing interest The authors affirm that they have no known competing financial interests or interpersonal conflicts that might have an impact on the research presented in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The increase in antibiotic resistance promotes the situation of developing new antibiotics at the forefront, while the development of non-antibiotic pharmaceuticals is equally significant. In the post-antibiotic era, nanomaterials with high antibacterial efficiency and no drug resistance make them attractive candidates for antibacterial materials. Carbon dots (CDs), as a kind of carbon-based zero-dimensional nanomaterial, are attracting much attention for their multifunctional properties. The abundant surface states, tunable photoexcited states, and excellent photo-electron transfer properties make sterilization of CDs feasible and are gradually emerging in the antibacterial field. This review provides comprehensive insights into the recent development of CDs in the antibacterial field. The topics include mechanisms, design, and optimization processes, and their potential practical applications are also highlighted, such as treatment of bacterial infections, against bacterial biofilms, antibacterial surfaces, food preservation, and bacteria imaging and detection. Meanwhile, the challenges and outlook of CDs in the antibacterial field are discussed and proposed., (© 2023 Wiley-VCH GmbH.)

Objective: This study aimed to explore the clinical efficiency of an improved transosseous pullout suture technique for arthroscopic repair of a meniscus root tear., Methods: From January 2017 to January 2021, 53 patients with posterior meniscus root tears combined with anterior cruciate ligament (ACL) and/or posterior cruciate ligament (PCL) tears were collected. Totally, in 29 patients (group A), the 2.0 mm modified pullout tunnel method was used to suture the posterior meniscus root, while 24 patients (group B) were treated with the traditional 4.5 mm pullout tunnel method. In group A, 20 patients had lateral meniscus posterior root (LMPR) combined with ACL tears, 5 patients had LMPR combined with ACL and PCL tears, and 4 patients had medial meniscus posterior root (MMPR) combined with ACL tears. In group B, 19 patients had LMPR combined with ACL tears, 3 patients had LMPR combined with ACL and PCL tears, and 2 patients had MMPR combined with ACL tears. The improvement of the Lysholm and VAS scores and the incidence of complications in group A and group B before the operation, 1 month and 3 months after the operation, and after the final follow-up were compared., Results: Preoperative Lysholm score was 26.0±5.6 in group A and 26.7±5.8 in group B (P>0.05). One-month postoperative Lysholm score was 66.5±5.7 in group A and 54.3±2.4 in group B (P<0.001). Three-month postoperative Lysholm score was 81.1±7.2 in group A and 73.2±9.7 in group B (P<0.05). Lysholm scores after the final follow-up was 90.3±5.6 in group A and 90.0±5.0 in group B (P>0.05). Preoperative VAS score was 6.3±1.4 in group A and 6.3±1.2 in group B (P>0.05). One-month postoperative VAS score was 1.8±0.7 in group A and 2.4±0.9 in group B (P<0.05). Three-month postoperative VAS score was 0.7±0.6 in group A and 0.8±0.6 in group B (P>0.05). VAS score after the final follow-up was 0.2±0.4 in group A and 0.3±0.5 in group B (P>0.05)., Conclusion: The improved transosseous pullout suture technique using a smaller 2.0 mm bone tunnel can virtually eliminate the risk of conflict with other bone tunnels and facilitate the management of bone tunnels in multiple ligament injuries, while also diminishing suture abrasion caused by the windshield wiper effect. The technique achieves good clinical efficacy., (© 2023. Huazhong University of Science and Technology.)

Objective: To investigate the incidence of and factors influencing postoperative delirium (POD) in Parkinson disease after deep brain stimulation (DBS) surgery., Methods: A total of 272 patients with Parkinson disease who underwent DBS completed the Visual Impairment in Parkinson Disease Questionnaire (VIPD-Q) and underwent neuro-ophthalmologic examinations including optical coherence tomography and fundus vessel analysis. We retrospect the prevalence of POD in groups with different VIPD-Q scores, retinal nerve fiber layer (RNFL) thicknesses, and vessel percentage areas (VPA). A predictive model based on the VIPD-Q was constructed using multivariate logistic regression and verified using bootstrap validation., Results: POD was experienced by 65 (23.9%) of 272 patients. Patients with PD who had visual impairment (VIPD-Q > 6) had a higher incidence of POD (chi-square, P < 0.001). The thickness of the RNFL and VPA were also correlated with POD risk. Differences in implantation locations (subthalamic nucleus or pars interna of globus pallidus), operation times, and general anesthesia times did not affect the prevalence of DBS-related POD. A nomogram was constructed based on ophthalmic events to predict the risk of POD., Conclusions: The study findings provide convincing evidence of the relationship between visual dysfunction and the risk of POD. In view of the higher risk of POD, visually impaired patients with PD should undergo closer monitoring after DBS surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Targeting single tumor antigens makes it difficult to provide sufficient tumor selectivity for T cell engagers (TCEs), leading to undesirable toxicity and even treatment failure, which is particularly serious in solid tumors. Here, we designed novel trispecific TCEs (TriTCEs) to improve the tumor selectivity of TCEs by logic-gated dual tumor-targeting. TriTCE can effectively redirect and activate T cells to kill tumor cells (∼18 pM EC 50 ) by inducing the aggregation of dual tumor antigens, which was ∼70- or 750- fold more effective than the single tumor-targeted isotype controls, respectively. Further in vivo experiments indicated that TriTCE has the ability to accumulate in tumor tissue and can induce circulating T cells to infiltrate into tumor sites. Hence, TriTCE showed a stronger tumor growth inhibition ability and significantly prolonged the survival time of the mice. Finally, we revealed that this concept of logic-gated dual tumor-targeted TriTCE can be applied to target different tumor antigens. Cumulatively, we reported novel dual tumor-targeted TriTCEs that can mediate a robust T cell response by simultaneous recognition of dual tumor antigens at the same cell surface. TriTCEs allow better selective T cell activity on tumor cells, resulting in safer TCE treatment., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Time delay lighting offers an added period of buffer illumination for human eyes upon switching off the light. Long-lifetime emission from triplet excitons has outstanding potential, but the forbidden transition property due to the Pauli exclusion principle makes them dark, and it stays challenging to develop full-color and bright triplet excitons. Herein, triplet excitons emission from ultraviolet (UV) to near infrared (NIR) in carbon nanodots (CNDs) is achieved by confining multicolor CNDs emitters in NaCNO crystal. NaCNO crystal can isolate the CNDs, triplet excitons quenching caused by the excited state electrons aggregation induced energy transfer is suppressed, and the confinement crystal can furthermore promote phosphorescence of the CNDs by inhibiting the dissipation of the triplet excitons due to non-radiative transition. The phosphorescence from radiative recombination of triplet excitons in the CNDs covers the spectral region from 300 nm (UV) to 800 nm (NIR), the corresponding lifetimes can reach 15.8, 818.0, 239.7, 168.4, 426.4, and 127.6 ms. Furthermore, the eco-friendly luminescent lampshades are designed based on the multicolor phosphorescent CNDs, time delay light-emitting diodes are thus demonstrated. The findings will motivate new opportunities for the development of UV to NIR phosphorescent CNDs and time delay lighting applications., (© 2023 Wiley-VCH GmbH.)

Epidemic diseases of crops caused by fungi deeply affected the course of human history and processed a major restriction on social and economic development. However, with the enormous misuse of existing antimicrobial drugs, an increasing number of fungi have developed serious resistance to them, making the diseases caused by pathogenic fungi even more challenging to control. Drug repurposing is an attractive alternative, it requires less time and investment in the drug development process than traditional R&D strategies. In this work, we screened 600 existing commercially available drugs, some of which had previously unknown activity against pathogenic fungi. From the primary screen at a fixed concentration of 100 μg/mL, 120, 162, 167, 85, 102, and 82 drugs were found to be effective against Rhizoctonia solani, Sclerotinia sclerotiorum, Botrytis cinerea, Phytophthora capsici, Fusarium graminearum and Fusarium oxysporum, respectively. They were divided into nine groups lead compounds, including quinoline alkaloids, benzimidazoles/carbamate esters, azoles, isothiazoles, pyrimidines, pyridines, piperidines/piperazines, ionic liquids and miscellaneous group, and simple structure-activity relationship analysis was carried out. Comparison with fungicides to identify the most promising drugs or lead structures for the development of new antifungal agents in agriculture., (© 2023. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: Induction chemotherapy (IC) comprising docetaxel, cisplatin, and fluorouracil (TPF), combined with concurrent chemoradiotherapy (CCRT) effectively improves the survival rate of locally advanced nasopharyngeal carcinoma (LA-NPC). Selecting patients whose risk of tumor recurrence and metastasis is high and the appropriate chemotherapy intensity is a concern. We combined tumor-node-metastasis staging with the load of Epstein-Barr virus (EBV) after IC to select the individualized chemotherapy strength., Methods: The clinical data and prognostic factors of patients with stage III-IV LA-NPC treated with TPF IC combined with CCRT were analyzed retrospectively. The conventional treatment group received the standard three cycles TPF IC combined with CCRT. For the new treatment group, the cycles of IC were determined according to whether the EBV-DNA disappeared completely after a certain course of IC, if so, subsequent IC was stopped and the chemoradiotherapy stage was entered. Propensity score matching (PSM) was performed at a ratio of 1:1 to balance baseline characteristics. Survival outcomes and adverse events between the conventional treatment group and the new method treatment group were compared., Results: The study included 256 patients, among whom 192 were matched successfully into 96 pairs. The patients were followed up for a median of 51 months. The proportions of patients receiving three, two, and one cycle of IC after PSM in the routine and new treatment cohorts were 93.8%, 3.1%, 3.1% versus 21.9%, 49.0%, 24.0%, respectively. However, their 3-year distant metastasis-free survival, local recurrence-free survival, progression-free survival, and overall survival did not differ significantly. The incidence of grade 3-4 neutropenia toxicity in CCRT decreased significantly in patients receiving the new treatment method compared with that in the conventional treatment group (p = 0.026)., Conclusion: Combining TNM stage and EBV-DNA load after IC to determine the courses of IC in patients with LA-NPC did not alter the curative effect but decreased toxicity., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Phytopathogenic bacteria are a major cause of crop mortality and yield reduction, especially in field cultivation. The lack of effective chemistry agri-bactericides is responsible for challenging field prevention and treatment, prompting the development of long-lasting solutions to prevent, reduce, or manage some of the most devastating plant diseases facing modern agriculture today and in the future. Therefore, there is an urgent need to find lead drugs preventing and treating phytopathogenic bacterial infection. Drug repurposing, a strategy used to identify novel uses for existing approved drugs outside of their original indication, takes less time and investment than Traditional R&D Strategies in the process of drug development. Based on this method, we conduct a screen of 700 chemically diverse and potentially safe drugs against Xanthomonas oryzae PV. oryzae ACCC 11602 (Xoo), Xanthomonas axonopodis PV. citri (Xac), and Pectobacterium atrosepticum ACCC 19901 (Pa). Furthermore, the structure-activity relationship and structural similarity analysis of active drugs classify potent agri-bactericides into 8 lead series: salicylanilides, cationic nitrogen-containing drugs, azole antifungals, N-containing group, hydroxyquinolines, piperazine, kinase inhibitor and miscellaneous groups. MIC values were evaluated as antibacterial activities in this study. Identifying highly active lead compounds from the screening of approved drugs and comparison with the currently applied plant pathogenic bactericide to validate the bactericidal activity of the best candidates and assess if selected molecules or scaffolds lead to develop new antibacterial agents in the future. In conclusion, this study provides a possibility for the development of potent and highly selective agri-bactericides leads., (© 2022. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: Human immunodeficiency virus type 1 (HIV-1) epidemic in China is featured by geographical diversity of epidemic patterns. Understanding the characteristics of regional HIV-1 epidemic allows carrying out targeted prevention and controlling measures. This seven-year cross-sectional study was conducted in Heilongjiang, one province of Northeast China, where newly diagnosed infection is fast increasing yearly, but temporal HIV-1 epidemic trend is largely unknown., Methods: Information of 1,006 newly diagnosed HIV-1-infected participants were collected before antiretroviral therapy during 2010-2016 in Heilongjiang province. HIV-1 genotype was identified based on the viral gag and env gene sequences. Recent infection was determined by Limiting-Antigen Avidity assays. Comparison analyses on the median ages, CD4 counts, proportions of stratified age groups and CD4 count groups, and rates of recent HIV-1 infection among different population and sampling times were performed to understand temporal HIV-1 epidemic features., Results: Homosexual contact among men who have sex with men (MSM) was the main transmission route and CRF01&#95;AE was the most dominant HIV-1 genotype. During 2010-2016, the HIV-1 epidemic showed three new changes: the median age continued to decline, the cases with a CD4 count more than 500 cells/μl (CD4hi cases) disproportionally expanded, and the recent HIV-1 infection rate steadily increased. MSM cases determined the temporal trend of HIV-1 epidemic here. Increase of young MSM cases (aged <30 years) made the main contribution to the younger age trend of MSM cases. These young MSM exhibited a higher median CD4 count, a higher proportion of CD4hi cases, and a higher rate of recent HIV-1 infection than cases aged 30 years and more. MSM infected by CRF01&#95;AE virus mostly affected HIV-1 epidemic patterns among MSM population., Conclusion: Young MSM have become a new hotspot and vulnerable group for HIV-1 transmission in Heilongjiang Province, Northeast China. The rapid increase in the number of young MSM cases, mainly those with CRF01&#95;AE infection, changed temporal HIV-1 epidemic pattern here. Measures for prevention and control of HIV-1 infection among this population are urgently needed in the future., 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 © 2022 Li, Wang, Liu, Zhang, Li, Wang, Zhang, Zhao, Liu, Chen and Wang.)

Objective: Visual impairment is a common non-motor symptom (NMS) in patients with Parkinson's disease (PD) and its implications for cognitive impairment remain controversial. We wished to survey the prevalence of visual impairment in Chinese Parkinson's patients based on the Visual Impairment in Parkinson's Disease Questionnaire (VIPD-Q), identify the pathogens that lead to visual impairment, and develop a predictive model for cognitive impairment risk in Parkinson's based on ophthalmic parameters., Methods: A total of 205 patients with Parkinson's disease and 200 age-matched controls completed the VIPD-Q and underwent neuro-ophthalmologic examinations, including ocular fundus photography and optical coherence tomography. We conducted nomogram analysis and the predictive model was summarized using the multivariate logistic and LASSO regression and verified via bootstrap validation., Results: One or more ophthalmologic symptoms were present in 57% of patients with Parkinson's disease, compared with 14% of the controls (χ 2 -test; p < 0.001). The visual impairment questionnaire showed good sensitivity and specificity (area under the curve [AUC] = 0.918, p < 0.001) and a strong correlation with MoCA scores (Pearson r = -0.4652, p < 0.001). Comparing visual impairment scores between pre- and post-deep brain stimulation groups showed that DBS improved visual function ( U -test, p < 0.001). The thickness of the retinal nerve fiber layer and vessel percentage area predicted cognitive impairment in PD., Interpretation: The study findings provide novel mechanistic insights into visual impairment and cognitive decline in Parkinson's disease. The results inform an effective tool for predicting cognitive deterioration in Parkinson's based on ophthalmic parameters., 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 © 2022 Zhang, Wu, Hou, Wang, Zhang, Zhao, Wang, Wang and Li.)

The inhibitory effect of tavaborole on the invasion of Botrytis cinerea in grapes and tomatoes, as well as the potential mechanism involved, was discovered in this study. Our findings showed that tavaborole inhibited Botrytis cinerea spore germination and mycelial expansion in vitro and that the control efficiency in vivo on fruit decay was dose-dependent, which was effective in reducing disease severity and maintaining the organoleptic quality of the fruit, such as reducing weight loss and retaining fruit hardness and titratable acid contents during storage. Furthermore, the precise mechanism of action was investigated further. Propidium iodide staining revealed that Botrytis cinerea treated with tavaborole lost membrane integrity. For further validation, cytoplasmic malondialdehyde accumulation and leakage of cytoplasmic constituents were determined. Notably, the inhibitory effect was also dependent on inhibiting the activities of aminoacyl-tRNA synthetases involved in the aminoacyl-tRNA biosynthesis pathway in Botrytis cinerea . The above findings concluded that tavaborole was effective against Botrytis cinerea infection in postharvest fruit, and a related mechanism was also discussed, which may provide references for the drug repurposing of tavaborole as a postharvest fungicide.

Formaldehyde (FA) serves as a prevailing air pollutant, which has seriously threatened public health in recent years. Of all the known health effects, lung injury is one of the most severe risks. However, little is known about the circRNAs related molecular mechanism in the development of lung injury induced by FA. This study was designed to explore the potential roles of dysregulated circRNAs as well as its mechanism in FA-induced lung injury. In the present study, 24 male SD rats were exposed to formaldehyde (control, 0.5, 2.46 and 5 mg/m 3 ) for 8 h per day for 8 weeks to induce lung injury. We used H&E staining to evaluate the histopathological changes of lung injury indifferent groups. The expression of circRNAs in lung tissue was detected by real-time PCR. Meanwhile, circRNA/miRNA/mRNA interaction networks were predicted by bioinformatics analysis. Our study revealed that formaldehyde exposure resulted in abnormal histopathological changes in lung tissues. Moreover, the expression of rno&#95;circRNA&#95;008646 was significantly higher in lung tissues of formaldehyde exposure rats than in control. Bioinformatics analysis showed that one potential target miRNA/mRNA for rno&#95;circRNA&#95;008646 was rno-miR-224/Forkhead Box I1 (FOXI1). Besides, luciferase report gene confirmed that there was targeted binding relationship between rno&#95;circRNA&#95;008646 and rno-miR-224, rno-miR-224 and FOXI1. Further verification experiments indicated that the expression of rno&#95;circRNA&#95;008646 was negatively correlated rno-miR-224, while it was positively correlated with FOXI1. JASPAR database showed transcription factor FOXI1 located in promotor of CF Transmembrane Conductance Regulator (CFTR). Both FOXI1 and CFTR were up-regulated in lung tissues after formaldehyde exposure. In conclusion, our findings suggested that formaldehyde may induce lung injury, and this may be caused by up-regulatedrno&#95;circRNA&#95;008646, which medicated rno-miR-224/FOXI1/CFTR axis., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

The microbial spoilage of soybeans during soaking process severely deteriorates the quality of soybean products and threatens human health. Herein, water-soluble aminated zinc oxide nanoparticles (ZnO NPs) were developed to effectively control the microbial spoilage in soybeans during soaking. ZnO NPs achieved significant inactivation of three dominant spoilage bacteria (bacillus cereus, bacillus megaterium and enterococcus faecium) isolated from the deteriorated soybeans, which could adhere to the bacterial surface and damage the cell wall/membrane, but also generate large amounts of reactive oxygen species (ROS). Compared to two commercial ZnO, water-soluble ZnO exhibited superior antibacterial properties due to producing more ROS and bacteria-adhered ability. After ZnO NPs treatment, the content of the residual Zn (51.1 mg/kg) in soybeans was the safety standards of Zn element in soybeans products for human). Therefore, the water-soluble ZnO NPs showed great potentials as efficient and safe antimicrobial agents for soybeans preservation during soaking process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Importance: The potential effects of long-term occupational exposure to formaldehyde (FA) on human semen quality is not clear., Objective: To assess whether long-term occupational exposure to FA is associated with semen quality., Design, Setting, and Participants: This population-based cohort study was conducted from June 1 to June 30, 2021, in Xi'an, China. Participants were adults aged 23 to 40 years who had lived in the study area for 24 months or longer. Data analysis was performed from September 1 to October 1, 2021., Exposures: Long-term occupational exposure to FA was measured using a formaldehyde detector, and the FA exposure index (FEI) was calculated as follows: FEI = final concentration of FA (mg/m3) × work time during a workday (hour) × cumulative workdays (year)., Main Outcomes and Measures: Semen samples were collected by masturbation after 3 to 7 days of abstinence and were then assessed by the computer-automated semen analysis system, Baso-Papanicolaou staining, and sperm-chromatin structure assay., Results: A total of 205 men (mean [SD] age, 29.49 [3.64] years), with 124 individuals in the FA exposure group (mean [SD] FEI, 73.72 [54.86]) and 81 age-matched controls, were included in the final analysis. Long-term personal occupational exposure to FA was significantly associated with poor semen quality. Specifically, a 1-unit increase in FEI was associated with a change of -0.99% (95% CI, -1.00% to -0.98%) in total sperm motility, -0.99% (95% CI, -0.99% to -0.97%) in progressive sperm motility, -0.05% (95% CI, -0.08% to -0.02%) in curvilinear velocity, -0.07% (95% CI, -0.10% to -0.04%) in straight line velocity, -0.07% (95% CI, -0.10% to -0.04%) in time-average velocity, -0.98% (95% CI, -0.99% to -0.93%) in normal sperm morphology, -0.24% (95% CI, -0.35% to -0.11%) in seminal neutral glucosidase, -0.61% (95% CI, -0.66% to -0.56%) in seminal plasma zinc, 0.52% (95% CI, 0.15% to 1.02%) in beat cross frequency, and 0.10% (95% CI, 0.06% to 0.14%) in the DNA fragmentation index. These associations remained significant after adjusting for confounding factors. Furthermore, subgroup analysis found that high levels of oxidative stress might promote the associations between FA exposure and semen quality., Conclusions and Relevance: This study found an association between long-term occupational exposure to FA and semen quality. This deterioration was dose and time dependent and might be induced by oxidative stress.

The application of high hydrostatic pressure (HHP) technology in the food industry has generated potential safety hazards due to sub-lethally injured (SI) pathogenic bacteria in food products. To address these problems, this study explored the repair mechanisms of HHP-induced SI Escherichia coli O157:H7. First, the repair state of SI E. coli O157:H7 (400 MPa for 5 min) was identified, which was cultured for 2 h (37 °C) in a tryptose soya broth culture medium. We found that the intracellular protein content, adenosine triphosphate (ATP) content, and enzyme activities (superoxide dismutase, catalase, and ATPase) increased, and the morphology was repaired. The transcriptome was analyzed to investigate the molecular mechanisms of SI repair. Using cluster analysis, we identified 437 genes enriched in profile 1 (first down-regulated and then tending to be stable) and 731 genes in profile 2 (up-regulated after an initial down-regulation). KEGG analysis revealed that genes involved in cell membrane biosynthesis, oxidative phosphorylation, ribosome, and aminoacyl-tRNA biosynthesis pathways were enriched in profile 2, whereas cell-wall biosynthesis was enriched in profile 1. These findings provide insights into the repair process of SI E. coli O157:H7 induced by HHP.

Background: P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications. The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric patients with epilepsy., Methods: The serum concentrations of LCM were determined by ultrahigh performance liquid chromatography, and the ABCB1 polymorphism was analyzed through polymerase chain reaction-fluorescence staining in situ hybridization. The χ2 test and the Fisher exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the one-way analysis of variance and the Mann-Whitney test., Results: A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (P < 0.05, OR = 1.966, 95% CI, 1.060-3.647). Patients with the G2677T/A-AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 versus 0.8 ± 0.5 mcg/mL per mg/kg, P < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (P = 0.008 and P = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (P = 0.042)., Conclusions: ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Triplet excitons usually do not emit light under ambient conditions due to the spin-forbidden transition rule, thus they are called dark excitons. Herein, triplet excitons in carbon nanodots (CNDs) are brightened by embedding the CNDs into poly(vinyl alcohol) (PVA) films; flexible multicolor phosphorescence films are thus demonstrated. PVA chains can isolate the CNDs, and excited state electron or energy transfer induced triplet exciton quenching is thus reduced; while the formed hydrogen bonds between the CNDs and PVA can restrict vibration/rotation of the CNDs, thus further protecting the triplet excitons from nonradiative recombination. The lifetimes of the flexible multicolor phosphorescence films can reach 567, 1387, 726, and 311 ms, and the longest-lasting phosphorescence film can be observed by naked eyes for nearly 15 s even after bending 5000 times. The phosphorescence films can be processed into various patterns, and a dynamic optical signature concept has been proposed and demonstrated based on the phosphorescence films.

Phosphorescent carbon nanodots (CNDs) have generated enormous interest recently, and the CND phosphorescence is usually located in the visible region, while ultraviolet (UV) phosphorescent CNDs have not been reported thus far. Herein, the UV phosphorescence of CNDs was achieved by decreasing conjugation size and in-situ spatial confinement in a NaCNO crystal. The electron transition from the p x to the sp 2 orbit of the N atoms within the CNDs can generate one-unit orbital angular momentum, providing a driving force for the triplet excitons population of the CNDs. The confinement caused by the NaCNO crystal reduces the energy dissipation paths of the generated triplet excitons. By further tailoring the size of the CNDs, the phosphorescence wavelength can be tuned to 348 nm, and the room temperature lifetime of the CNDs can reach 15.8 ms. As a demonstration, the UV phosphorescent CNDs were used for inactivating gram-negative and gram-positive bacteria through the emission of their high-energy photons over a long duration, and the resulting antibacterial efficiency reached over 99.9%. This work provides a rational design strategy for UV phosphorescent CNDs and demonstrates their novel antibacterial applications., (© 2022. The Author(s).)

Objectives: Our study aimed to investigate the relationship between the severity of frailty and the long-term care (LTC) needs of older adults from Chinese communities., Design: A cross-sectional study., Setting: Three Chinese community health centres. All data were collected by trained researchers through face-to-face collection., Participants: We surveyed a total of 540 older residents who aged 60 or older from community in Guangzhou, China., Measures: The Chinese version of the Tilburg frailty indicator was used to assess the frailty status of participants. LTC needs was evaluated by Integrated Home Care Services Questionnaire. Using non-adjusted and multivariate adjusted logistic regression analysis to evaluate frailty and LTC needs, then smoothed plots, threshold effect analysis and P for trend were used to further investigate the relationship between them., Results: The prevalence of frailty was 45.2% among the 540 older adults enrolled (aged 70.4±8.3 years; 65.7% females). 27% had higher LTC needs, which increased to 65.1% for individuals with frailty. Logistic regression analysis showed that frailty was strongly associated with LTC needs (OR 3.06, 95% CI 2.06 to 4.55, p<0.01). In the multivariate model, after adjusting for demographic characteristics, economic situation, activities of daily living and comorbidities, frailty remained significantly associated with LTC needs (OR 2.32, 95% CI 1.39 to 3.88, p<0.01). The smoothed plots showed a nearly linear relationship between frailty and LTC needs. Threshold effect analysis showed that every point increase in frailty, the score of LTC needs increased 1.3 points. The IQR to regroup individuals with frailty. Compared with the first quartile (scores ≤2), the incidence of LTC needs increased with the frailty status (p value for trend <0.01)., Conclusion: There is a linear relationship between frailty and LTC needs. With the increasing degree of frailty, the LTC needs of older adults dramatically increases., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The increasing resistance of plant diseases caused by phytopathogenic fungi highlights the need for highly effective and environmentally benign agents. The antifungal activities of Cnidium monnieri fruit extracts and five isolated compounds as well as structurally related coumarins against five plant pathogenic fungi were evaluated. The acetone extract, which contained the highest amount of five coumarins, showed strongest antifungal activity. Among the coumarin compounds, we found that 4-methoxycoumarin exhibited stronger and broader antifungal activity against five phytopathogenic fungi, and was more potent than osthol. Especially, it could significantly inhibit the growth of Rhizoctonia solani mycelium with an EC 50 value of 21 μg mL -1 . Further studies showed that 4-methoxycoumarin affected the structure and function of peroxisomes, inhibited the β-oxidation of fatty acids, decreased the production of ATP and acetyl coenzyme A, and then accumulated ROS by damaging MMP and the mitochondrial function to cause the cell death of R. solani mycelia. 4-Methoxycoumarin presented antifungal efficacy in a concentration- dependent manner in vivo and could be used to prevent the potato black scurf. This study laid the foundation for the future development of 4-methoxycournamin as an alternative and friendly biofungicide., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Water-soluble red afterglow imaging agents based on ecofriendly nanomaterials have potential application in time-gated afterglow bioimaging due to their larger penetration depth and nondurable excitation. Herein, red afterglow imaging agents consisted of Rhodamine B (RhB) and carbon nanodots (CNDs) have been designed and demonstrated. In these agents, CNDs act as energy donors, and RhB acts as an energy acceptor. Both of them are confined into a hydrophilic silica shell to form a CNDs-RhB@silica nanocomposite. The phosphorescence emission spectrum of the CNDs and the absorption spectrum of the RhB match well, and efficient energy transfer from the CNDs to the RhB via Förster resonant energy transfer process can be achieved, with a transfer efficiency can reach 99.2%. Thus, the as-prepared nanocomposite can emit a red afterglow in aqueous solution, and the afterglow spectrum of CNDs-RhB@silica nanocomposite can extend to the first near-infrared window (NIR-I). The luminescence lifetime and afterglow quantum yield (QY) of the CNDs-RhB@silica can reach 0.91 s and 3.56%, respectively, which are the best results in red afterglow region. Time-gated in vivo afterglow imaging has been demonstrated by using the CNDs-RhB@silica as afterglow agents.

Humulus lupulus Linn. is a traditional medicinal and edible plant with several biological properties. The aims of this work were: (1) to evaluate the in vitro antifungal activity of H. lupulus ethanolic extract; (2) to study the in vitro and in vivo antifungal activity of isoxanthohumol, an isoprene flavonoid from H. lupulus , against Botrytis cinerea ; and (3) to explore the antifungal mechanism of isoxanthohumol on B. cinerea . The present data revealed that the ethanolic extract of H. lupulus exhibited moderate antifungal activity against the five tested phytopathogenic fungi in vitro, and isoxanthohumol showed highly significant antifungal activity against B. cinerea , with an EC 50 value of 4.32 µg/mL. Meanwhile, it exhibited moderate to excellent protective and curative efficacies in vivo. The results of morphologic observation, RNA-seq, and physiological indicators revealed that the antifungal mechanism of isoxanthohumol is mainly related to metabolism; it affected the carbohydrate metabolic process, destroyed the tricarboxylic acid (TCA) cycle, and hindered the generation of ATP by inhibiting respiration. Further studies indicated that isoxanthohumol caused membrane lipid peroxidation, thus accelerating the death of B. cinerea . This study demonstrates that isoxanthohumol can be used as a potential botanical fungicide for the management of phytopathogenic fungi.

An europium functionalized ZnO quantum dots (QDs) ratiometric fluorescent nanoprobe is designed to establish a real time, on-site visual, and highly sensitive probe method for tetracycline (TC). The yellow-emitting ZnO QDs serves as the internal reference, while the Eu 3+ chelated on the surface of ZnO QDs is used as the signal reporting unit. This nanoprobe exhibits rapid response, excellent selectivity, and high sensitivity with a detection limit of 4 nM in detecting the levels of TC. In addition, fluorescence of the nanoprobe can change from yellow to red as the concentration of TC increases. Thus, naked eye detection of TC was realized using the test paper processed by nanoprobe, followed by RGB value analysis function on the mobile phone APP., 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 © 2021 Elsevier B.V. All rights reserved.)

The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future. The receptor binding domain (RBD), located at the S protein of SARS-CoV-2, contains most of the neutralizing epitopes. However, the immunogenicity of RBD monomers is not strong enough. In this study, we fused the RBD-monomer with a modified Fc fragment of human IgG1 to form an RBD-Fc fusion protein. The recombinant vaccine candidate based on the RBD-Fc protein could induce high levels of IgG and neutralizing antibody in mice, and these could last for at least three months. The secretion of IFN-γ, IL-2 and IL-10 in the RBD-stimulated splenocytes of immunized mice also increased significantly. Our results first showed that the RBD-Fc vaccine could induce both humoral and cellular immune responses and might be an optional strategy to control COVID-19.

Objective: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy., Methods: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted., Results: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period., Conclusion: HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883)., (© 2021. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Although circular RNAs (circRNAs) can function as microRNAs (miRNAs) sponges to participate in spermatogenesis, little is known about the functions of circRNAs in testis exposed to formaldehyde. In this study, twenty-four male SD rats (6-8 weeks) were randomly assigned to four groups, including a control group, 0.5, 2.46, and 5 mg/m 3 formaldehyde exposure groups, inhaling formaldehyde for eight consecutive weeks. The RT-qPCR was used to detect the expression of rno&#95;circRNA&#95;016194; the testicular injuries were observed by testicular histopathology. Our study illustrated up-regulated rno&#95;circRNA&#95;016194 was dose-dependent with formaldehyde. Simultaneously, the testicular histopathology showed an obvious damages in the 2.46 and 5 mg/m 3 formaldehyde exposure rats. Combined with bioinformatics analysis, the rno-miR-449a-5p was predicted and verified that its expression decreased in the testis exposed to formaldehyde. Meanwhile, the testicular morphometry changes were contrary to the expression of rno&#95;circRNA&#95;016194 and consistent with rno-miR-449a-5p. Moreover, bioinformatics analysis also prompted the potential downstream target gene for rno&#95;circRNA&#95;016194/rno-miR-449a-5p was Atg4b, and Atg4b expression was up-regulated in rats exposed to formaldehyde verifying by Western blot. Collectively, the rno&#95;circRNA&#95;016194 might be involved in formaldehyde-induced male reproductive toxicity and become potential therapeutic targets for male occupational exposure to formaldehyde., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Regional citrate anticoagulation (RCA) for renal replacement therapy is widely practiced in critically ill patients. However, concern exists regarding its labor-intensiveness for monitoring and the associated hypocalcemia. In this study, we provided an algorithm for prescribing RCA and evaluated its safety in patients., Methods: During 18 hemofiltration treatments with calcium-free replacement solution, participants were randomized to receive algorithm-based or trial-and-error RCA protocol. The effluent volume, post-filter and in vivo ionized calcium (iCa), and calcium in the sera and effluents were periodically measured at an interval of 1 to 2 h., Results: For patients received algorithm-based RCA protocol, no one had a serum iCa less than 0.9 mmol/L, and none needed calcium supplement adjustment to maintain serum calcium stability. For patients accepted trial-and-error protocol, all patients had a serum iCa below 0.9 mmol/L, their serum iCa and calcium levels fluctuated dramatically, and all patients need additional calcium supplement adjustment during RCA. None of the participants showed a post-filter iCa > 0.4 mmol/L., Conclusion: We provided a safe algorithm for calculating calcium supplementation doses that could maintain serum calcium stability without additional adjustment during RCA.

Aim: To identify the alterations of N6-methyladenosine (m 6 A) RNA profiles in cisplatin-induced acute kidney injury (Cis-AKI) in mice. Materials and Methods: The total level of m 6 A and the expression of methyltransferases and demethylases in the kidneys were measured. The profiles of methylated RNAs were determined by the microarray method. Bioinformatics analysis was performed to predict the functions. Results: Global m 6 A levels were increased after cisplatin treatment, accompanied by the alterations of Mettl3, Mettl14, Wtap, Fto, and Alkbh5. A total of 618 mRNAs and 98 lncRNAs were significantly differentially methylated in response to cisplatin treatment. Bioinformatics analysis indicated that the methylated mRNAs predominantly acted on the metabolic process. Conclusion: M 6 A epitranscriptome might be significantly altered in Cis-AKI, which is potentially implicated in the development of nephrotoxicity., 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 © 2021 Li, Li, Zhao, Ye and Peng.)

The specific recognition of T cell receptors (TCR) and peptides presented by human leukocyte antigens (pHLAs) is the core step for T cell triggering to execute anti-tumor activity. However, TCR assembly and soluble expression are challenging, which precludes the broad use of TCR in tumor therapy. Herein, we used heterodimeric Fc to assist in the correct assembly of TCRs to achieve the stable and soluble expression of several TCRs in mammalian cells, and the soluble TCRs enable us to yield novel bispecific T cell engagers (TCR/aCD3) through pairing them with an anti-CD3 antibody. The NY-ESO-1/LAGE-1 targeted TCR/aCD3 (NY-TCR/aCD3) that we generated can redirect naïve T cells to specific lysis antigen-positive tumor cells, but the potency of the NY-TCR/aCD3 was disappointing. Furthermore, we found that the activation of T cells by NY-TCR/aCD3 was mild and unabiding, and the activity of NY-TCR/aCD3 could be significantly improved when we replaced naïve T cells with pre-activated T cells. Therefore, we employed the robust T cell activation ability of staphylococcal enterotoxin C2 (SEC2) to optimize the activity of NY-TCR/aCD3. Moreover, we found that the secretions of SEC2-activated T cells can promote HLA-I expression and thus increase target levels, which may further contribute to improving the activity of NY-TCR/aCD3. Our study described novel strategies for soluble TCR expression, and the optimization of the generation and potency of TCR/aCD3 provided a representative for us to fully exploit TCRs for the precision targeting of cancers.