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Purpose: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions., Methods: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats., Results: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC 0-t 1.54 times higher than the reference formulation (Celebrex ® ). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug's half-life in vivo., Conclusion: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug's in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2024 Zhu et al.)

Background: Early enteral nutrition (EN) is recommended for sepsis management, but its optimal timing and clinical benefits remain uncertain. This study evaluates whether early EN improves outcomes compared to delayed EN in patients with sepsis., Methods: We analyzed data of septic patients from the MIMIC-IV 2.2 database, focusing on those in the Medical Intensive Care Unit (MICU) and Surgical Intensive Care Unit (SICU). Patients who initiated EN within 3 days were classified into the early EN group, while those who started EN between 3 and 7 days were classified into the delayed EN group. Propensity score matching was used to compare outcomes between the groups., Results: Among 1,111 patients, 786 (70.7%) were in the early EN group and 325 (29.3%) were in the delayed EN group. Before propensity score matching, the early EN group demonstrated lower mortality (crude OR = 0.694; 95% CI: 0.514-0.936; p = 0.018) and shorter ICU stays (8.3 [5.2, 12.3] vs. 10.0 [7.5, 14.2] days; p < 0.001). After matching, no significant difference in mortality was observed. However, the early EN group had shorter ICU stays (8.3 [5.2, 12.4] vs. 10.1 [7.5, 14.2] days; p < 0.001) and a lower incidence of AKI stage 3 (49.3% vs. 55.5%; p = 0.030). Subgroup analysis revealed that early EN significantly reduced the 28-day mortality rate in sepsis patients with lactate levels ≤4 mmol/L, with an adjusted odds ratio (aOR) of 0.579 (95% CI: 0.361, 0.930; p = 0.024)., Conclusion: Early enteral nutrition may not significantly reduce overall mortality in sepsis patients but may shorten ICU stays and decrease the incidence of AKI stage 3. Further research is needed to identify specific patient characteristics that benefit most from early EN., 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 © 2024 Xu, Xu, Ma, Xu, Gu, Lu and Wang.)

Acute ischemic stroke (AIS), commonly known as stroke, is a debilitating condition characterized by the interruption of blood flow to the brain, resulting in tissue damage and neurological deficits. Early diagnosis is crucial for effective intervention and management, as timely treatment can significantly improve patient outcomes. Therefore, novel methods for the early diagnosis of AIS are urgently needed. Several studies have shown that bioactive molecules contained in extracellular vesicles, especially circRNAs, could be ideal markers for the diagnosis of many diseases. However, studies on the effects of exosomes and their circRNAs on the development and prognosis of AIS have not been reported extensively. Therefore, we explored the feasibility of using circRNAs in plasma brain-derived exosomes as biomarkers for AIS. By high-throughput sequencing, we first identified 358 dysregulated circRNAs (including 23 significantly upregulated circRNAs and 335 significantly downregulated circRNAs) in the plasma brain-derived exosomes of the brain infarct patient group compared to those of the noninfarct control group. Five upregulated circRNAs (hsa&#95;circ&#95;0007290, hsa&#95;circ&#95;0049637, hsa&#95;circ&#95;0000607, hsa&#95;circ&#95;0004808, and hsa&#95;circ&#95;0000097) were selected for further validation via Real-Time Quantitative Reverse Transcription PCR (qRT‒PCR) in a larger cohort based on the exclusion criteria of log2FC > 1, p < 0.05 and measurable expression. We found that the expression levels of hsa&#95;circ&#95;0007290, hsa&#95;circ&#95;0049637, hsa&#95;circ&#95;0000607, hsa&#95;circ&#95;0004808 and hsa&#95;circ&#95;0000097 were significantly upregulated in AIS patients and could serve as potential biomarkers for AIS with high specificity and sensitivity. Moreover, the expression levels of hsa&#95;circ&#95;0007290, hsa&#95;circ&#95;0049637, hsa&#95;circ&#95;0000607, hsa&#95;circ&#95;0004808 and hsa&#95;circ&#95;0000097 were also found to be positively correlated with National Institutes of Health Stroke Scale (NISS) and modified Rankin scale (mRS) scores, which indicated that the presence of these circRNAs in plasma brain-derived exosomes could also determine the progression of AIS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Microneedles (MNs) prepared from polymeric materials are painless and minimally invasive, safe and efficient, but they hindered by low mechanical strength and single diverse drug release pattern. Due to the distinctive mechanical strength and dimensions of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), the integration of nano-technology with microneedles can effectively improve penetration and delivery efficiency through the stratum corneum. We herein designed a simple paroxetine (PAX)-loaded PLGA nanoparticles-integrated dissolving microneedles system (PAX-NPs-DMNs), aiming to improve the bioavailability of PAX through the synergistic permeation-enhancing effect of dissolving microneedles (DMNs) and NPs. PAX-NPs-DMNs had a complete tips molding rate (N eff ) of (94.06 ± 2.16) %, a 15×15 quadrangular-conical microneedle array and an overall fracture force of 301.10 N, which were improved nearly 0.50 times compared with the blank microneedles (HA-DMNs) and PAX microneedles (PAX-DMNs). PAX-NPs-DMNs could extend the release duration of PAX from 1 h to 24 h and the cumulative permeability per unit area (Q n ) was 47.66 times and 7.37 times higher than the PAX and the PAX-DMNs groups. PAX-NPs-DMNs could be rapidly dissolved within 10 min without hindering skin healing or causing adverse reactions. This study confirmed that PAX-NPs-DMNs can effectively improve the bioavailability of PAX and the mechanical strength of DMNs, which can easily penetrate the skin to provide sustained and painless delivery without causing adverse effects, thus offering a more convenient and effective method for central nervous diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest in this work., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Osteoarthritis causes tremendous damage to the joints, reducing the quality of life and imposing significant financial burden. An implantable drug-delivery system can improve the symptomatic manifestations with low doses and frequencies. However, the free drug has short retention in the joint cavity. Materials & methods: This study used electrostatic spinning technology to create an implantable drug-delivery system loaded with celecoxib (celecoxib nanofibers [Cel-NFs]) to improve retention and bioavailability. Results: Cel-NFs exhibited good formability, hydrophilicity and tensile properties. Cel-NFs were able to continuously release drugs for 2 weeks and increase the uptake capacity of Raw 264.7 cells, ultimately ameliorating symptoms in osteoarthritis rats. Conclusion: These results suggest that Cel-NFs can effectively ameliorate cartilage damage, reduce joint pain and alleviate osteoarthritis progression.

Flexible conductive hydrogels have great potential for healthcare and human motion sensing. However, it is difficult to simultaneously achieve conductive hydrogel epidermal sensors with reliable adhesion capabilities and excellent sensing properties, as well as accelerated wound healing performance in wearable hydrogels. Here, an epidermal sensor with excellent adhesion (0.6 kPa) and tensile strain (218.0 %) properties was assembled from an easy-to-prepare bilayer antimicrobial hydrogel, which effectively accelerates wound healing, as well as for human motion sensing. The upper hydrogel layer was composed of PVA, which could effectively enhance the mechanical properties of the bilayer hydrogel. The lower hydrogel layer consisted of polyacrylamide (PAm) and chitosan-dopamine (CC-DA). PAm with good adhesion properties adhered effectively to the skin surface. CC-DA not only had adhesion properties, but also has good antibacterial effects. It inhibited the growth of bacteria, which assisted in wound healing and infection prevention. Therefore, the design of the bilayer hydrogel combined the mechanical enhancement of PVA with the adhesion properties and antimicrobial effect of PAm and CC-DA to provide better wound repair. In addition, the double-layer hydrogel with good electrical conductivity (1.65 S·m -1 ) could sensitively monitor the tiny electrophysiological signals emitted by the human body during exercise rehabilitation training., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To compare the oncological survival outcomes of partial colectomy (PC) and hemicolectomy (HC) in patients with stage II colon cancer. A total of 18,795 patients with stage II colon cancer who underwent hemicolectomy (n = 12,022) or partial colectomy (n = 6773) from 2010 to 2019 were included in the the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were compared between the two groups, and the threshold of harvested lymph nodes was determined. The results showed that age, gender, race, tumor site, scope of regional lymph nodes, postoperative chemotherapy, postoperative radiotherapy, harvested lymph nodes, and tumor size were significantly different between the PC and HC groups (all P < 0.05). The OS rate was slightly lower in hemicolectomy patients than in partial colectomy patients (69.9% vs. 74.5%, respectively, P < 0.001), but CSS was similar between the two groups (87.9% vs. 88.1%, respectively, P = 0.32). After propensity score matching (PSM) was performed, the OS and CSS rates in the two groups were significantly different (CSS 84.3% vs. 88.0%, P < 0.001; OS 62.2% vs. 72.5%, P < 0.001). The survminer R package determined that the optimum threshold for the harvested lymph node count in stage II colon cancer patients was 16. CSS was significantly different between patients with ≥ 12 lymph nodes harvested and patients with ≥ 16 lymph nodes harvested (P = 0.043). Univariate and multivariate Cox regression and survival analyses of stage II colon cancer patients showed that the survival benefit of stage II colon cancer patients receiving partial colectomy was superior to that of patients receiving hemicolectomy. Partial colectomy has significant oncological benefits over hemicolectomy in the treatment of stage II colon cancer patients, even in the case of pT4b or tumor deposits. Removal of 16 lymph nodes during colectomy for stage II colon cancer correlated with improved survival, and this threshold was more effective than the standard threshold of 12 lymph nodes in distinguishing between patients with good and poor prognoses., (© 2023. Italian Society of Surgery (SIC).)

Objective: The chest computed tomography (CT) examination is an important clinical examination in the diagnosis and monitoring of paraquat- (PQ-) induced lung injury. The aim of this study was to explore the prognostic value of the average lung CT number acquired by quantitative CT techniques in patients with acute paraquat poisoning in the early stages of the disease., Methods: 46 patients who suffered from acute PQ poisoning in the emergency department of the Nanjing Drum Tower Hospital from January 2015 to June 2020 were enrolled in the present study. The patients were divided into survival group ( n  = 21) and nonsurvival group ( n  = 25). Clinical data were collected from subjects who met the inclusion criteria, including general information, personal disease history, and laboratory test indicators. The average lung CT numbers of each patient were obtained by quantitative CT techniques. Receiver operating characteristic (ROC) analysis was conducted to assess the prognostic value of average lung CT number in patients with acute paraquat poisoning., Results: The average CT numbers of the middle-lung, lower-lung, and whole lung fields in the nonsurvival group were significantly higher than those of the survival group ( p < 0.0001). However, the upper-lung field was not significantly different between the two groups ( p = 0.7765). The AUCs of different levels ranged from 0.554 to 0.977, among which the lower-lung field presented the largest AUC of 0.977 (95% CI: 0.943∼1; cut-off value: -702Hu; sensitivity 96%; specificity, 90.5%; YI: 0.865), followed by the whole lung field 0.914 (95% CI: 0.830∼0.999; cut-off value: -727Hu; sensitivity 76%; specificity, 95.2%; YI: 0.712) and the middle-lung field 0.87 (95% CI: 0.768∼0.971; cut-off value: -779Hu; sensitivity 80%; specificity, 85.7%; YI: 0.657)., Conclusion: The present study indicated that the average lung CT number could be used to evaluate the relationship between the severity of PQ-induced lung injury and prognosis, especially in the lower-lung field. However, further research is needed to draw a clear conclusion., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Xinrui Jiang et al.)

Background: Early evaluation of the severity of sepsis and estimation of its prognosis remains one of the main challenges in current therapeutic strategies. This study aimed to evaluate the prognostic value of plasma 7-ketocholesterol (7-KC) in sepsis., Methods: We retrospectively measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) the plasma 7-KC concentration in 176 patients with sepsis and 90 healthy volunteers. A multivariate Cox proportional hazard model was introduced to identify independent factors, including plasma 7-KC and clinical features, for the 28-day mortality of sepsis, and a nomogram for predicting the 28-day mortality of sepsis was established. Decision curve analysis (DCA) was performed to assess the prediction model of death risk of sepsis., Results: The area under the curve (AUC) of plasma 7-KC in diagnosing sepsis was 0.899 (95% CI = 0.862-0.935, P < 0.001), while it was 0.830 (95% CI = 0.764-0.894, P < 0.001) in diagnosing septic shock. The AUCs of plasma 7-KC in predicting the survival of sepsis patients in the training cohort and the test cohort were 0.770 (95% CI = 0.692-0.848, P < 0.05) and 0.869 (95% CI = 0.763-0.974, P < 0.05), respectively. In addition, high plasma 7-KC expression predicts poor prognosis in sepsis. Then, 7-KC and platelet count were identified as the two factors with significant differences by a multivariate Cox proportional hazard model, and the 28-day mortality probability ranged from 0.002 to 0.985 and was assessed using a nomogram. DCA results revealed that the combination of plasma 7-KC and platelet count showed the best prognostic efficiency of the risk threshold compared to a single factor in both the training cohort and test cohort., Conclusions: Collectively, the elevated plasma 7-KC level is an indicator of sepsis and was identified as a prognostic indicator for sepsis patients, providing a landscape for predicting survival in early sepsis with potential clinical utility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The tight structure of the blood-brain barrier severely limits the level of drug therapy for central nervous system disorders. In this study, a novel composite delivery system combining nanocarrier and microneedle technology was prepared to explore the possibility of transdermal delivery of drugs to work in the brain., Methods: Nanoparticle solutions containing paroxetine and rhodamine-B were prepared using PLGA as a carrier by the emulsification-solvent volatilization method. Then, they were mixed with hyaluronic acid and the PLGA nanoparticulate-based microneedle system (Rh-NPs-DMNs) was prepared by a multi-step decompression-free diffusion method. The particle size, zeta potential, and micromorphology of the nano solution were measured; the appearance, mechanical strength, dissolution properties, and puncture effect of the Rh-NPs-DMNs were evaluated; also, it was evaluated for in vivo live imaging properties and in vitro skin layer transport and distribution properties., Results: The mean particle size of Rh-NPs was 96.25 ± 2.26 nm; zeta potential of 15.89 ± 1.97 mV; PDI of 0.120 ± 0.079. Rh-NPs-DMNs had a high needle content of 96.11 ± 1.27% and a tip height of 651.23 ± 1.28 μm, with excellent mechanical properties (fracture force of 299.78 ± 1.74 N). H&E skin tissue staining showed that Rh-NPs-DMNs produced micron-sized mechanical pores approximately 550 μm deep immediately after drug administration, allowing for efficient circulation of the drug; and the results of in vivo imaging showed that Rh-B NPs DMNs had a faster transport rate than Rh-B DMNs, with strong fluorescent signals in both brain ( P <0.01) and hippocampus ( P <0.05) 48 h after drug administration., Conclusion: Nanoparticles can prolong blood circulation time and intracerebral retention time and have certain brain-targeting properties due to their excellent physical properties. The use of microneedle technology combined with nanocarriers provides new ideas for delivery systems for the treatment of central neurological diseases., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2023 Li et al.)

Although stem cell-based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)-abundant and hyper-inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO 2 @BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS-scavenging hydrogel (CeNP-Gel). CeNP-Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments and improving the viability of encapsulated NSCs. More interestingly, in the presence of CeNP-Gel, microglial polarization to anti-inflammatory M2 subtype are obviously facilitated, which is further verified to be associated with phosphoinositide 3-kinase/protein kinase B pathway activation. Additionally, the injectable ROS-scavenging hydrogel is confirmed to induce the integration and neural differentiation of transplanted NSCs. Compared with the blank-gel group, the survival rate of NSCs in CeNP-Gel group is about 3.5 times higher, and the neural differentiation efficiency is about 2.1 times higher. Therefore, the NSCs-laden ROS-scavenging hydrogel represents a comprehensive strategy with great application prospect for the treatment of SCI through comprehensively modulating the adverse microenvironment., (© 2023 Wiley-VCH GmbH.)

This study presents a method for a one-step co-encapsulation of PLGA nanoparticles in hydrophilic nanofibers. The aim is to effectively deliver the drug to the lesion site and achieve a longer release time. The celecoxib nanofiber membrane (Cel-NPs-NFs) was prepared by emulsion solvent evaporation and electrospinning with celecoxib as a model drug. By this method, nanodroplets of celecoxib PLGA are entrapped within polymer nanofibers during an electrospinning process. Moreover, Cel-NPs-NFs exhibited good mechanical strength and hydrophilicity, with a cumulative release of 67.74% for seven days, and the cell uptake at 0.5 h was 2.7 times higher than that of pure nanoparticles. Furthermore, pathological sections of the joint exhibited an apparent therapeutic effect on rat OA, and the drug was delivered effectively. According to the results, this solid matrix containing nanodroplets or nanoparticles could use hydrophilic materials as carriers to prolong drug release time.

Phosphatidylethanolamine-binding proteins (PEBP) family plays important roles in regulating plant flowering time and morphogenesis. However, geneme-wide identification and functional analysis of PEBP genes in the rigorous short-day plant Perilla frutescens ( PfPEBP ) have not been studied. In this study, 10 PfPEBP were identified and divided into three subfamilies based on their phylogenetic relationships: FT-like, TFL1-like and MFT-like. Gene structure analysis showed that all PfPEBP genes contain 4 exons and 3 introns. Motifs DPDxP and GIHR essential for anion-binding activity are highly conserved in PfPEBP. A large number of light-responsive elements were detected in promoter regions of PfPEBP . Gene expression of PfFT1 exhibited a diurnal rhythm. It was highly expressed in leaves under the short-day photoperiod, but higher in flowers and seeds under the long-day photoperiod. Overexpression of PfFT1 in Arabidopsis thaliana not only promoted early flowering of Col-0 or Ler, but also rescued the late flowering phenotype of ft-1 mutant. We concluded that PfFT1 promotes early flowering by regulating the expression of flowering-related genes AtAP1 , AtLFY , AtFUL and AtSOC1 . In conclusion, our results provided valuable information for elucidating the functions of PfPEBP in P . frutescens and shed light on the promoting effect of PfFT1 on flowering., 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 Xu, Guo, Hao, Lu, Li, Lu and Zhang.)

Background: Sepsis and septic shock, a subset of sepsis with higher risk stratification, are hallmarked by high mortality rates and necessitated early and accurate biomarkers., Methods: Untargeted metabolomic analysis was performed to compare the metabolic features between the sepsis and control systemic inflammatory response syndrome (SIRS) groups in discovery cohort, and potential metabolic biomarkers were selected and quantified using multiple reaction monitoring based target metabolite detection method., Results: Differentially expressed metabolites including 46 metabolites in positive electrospray ionization (ESI) ion mode, 22 metabolites in negative ESI ion mode, and 4 metabolites with dual mode between sepsis and SIRS were identified and revealed. Metabolites 5-Oxoproline, L-Kynurenine and Leukotriene D4 were selected based on least absolute shrinkage and selection operator regularization logistic regression and differential expressed between sepsis and septic shock group in the training and test cohorts. Respective risk scores for sepsis and septic shock based on a 3-metabolite fingerprint classifier were established to distinguish sepsis from SIRS, septic shock from sepsis. Significant relationship between developed sepsis risk scores, septic shock risk scores and Sequential (sepsis-related) Organ Failure Assessment (SOFA), procalcitonin (PCT) and lactic acid were observed., Conclusions: Collectively, our findings demonstrated that the characteristics of plasma metabolites not only manifest phenotypic variation in sepsis onset and risk stratification of sepsis but also enable individualized treatment and improve current therapeutic strategies., 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 Lu, Zhou, Yang, Li, Jiang, Zhang, Gu and Wang.)

Tumor cells can evade attack by phagocytes by upregulating the self-marker CD47. The mechanisms underlying tumor CD47 upregulation, however, remain unclear. Here, we report that human lung adenocarcinoma CD47 is upregulated by interferon-γ (IFN-γ), the level in the tumor microenvironment of which is markedly increased after tumor metastasis and chemotherapy. The IFN-γ receptor is expressed in various human lung adenocarcinoma tissues regardless of the CD47 protein expression, and lung adenocarcinoma CD47 expression is significantly enhanced following tumor metastasis or chemotherapy treatment. In line with this, CD47 expression in various lung cancer cells is markedly increased by IFN-γ treatment. Mechanistically, IFN-γ promotes CD47 expression by activating interferon regulatory factor-1 (IRF-1), which binds to an IRF-1-binding domain within the CD47 promoter region and increases CD47 transcription. Functionally, IFN-γ-enhanced CD47 expression facilitates human lung cancer cell invasion both in vitro and in vivo , whereas IFN-γ-induced CD47 upregulation and cancer metastasis are blocked by mutating the IRF-1-binding site within the CD47 promoter. Our results reveal IFN-γ-enhanced CD47 expression as a novel mechanism promoting human lung adenocarcinoma progression., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

In sludge disposal, Arsenic (As) poses serious secondary pollution due to its high toxicity and low stability. This work systematically studied the effects of Fenton-CaO composite conditioning on As chemistry throughout sludge dewatering, thermal drying, and steam gasification processes. The experimental results showed that, for raw sludge, 40.9% of As was released with filtrate discharging and 26.8-57.3% emitted with flue gas emission. When sludge was conditioned by Fenton-CaO, all of the As in the filtrate was fixed in the sludge cake and the releasing rate of gaseous As was reduced by up to 86.0%. Furthermore, the comprehensive results of the model compounds experiment, sequential extraction, and thermodynamic calculations revealed the effects of Fe/Ca conditioners on As species evolution. In the Fenton pre-oxidation, As(V) was reduced to As(III) due to the decreasing Eh caused by the excessive Fe(II). After adding CaO, As(III)/DMA (dimethyl arsenic) was adsorbed onto the surface of amorphous Fe(OH) 3 that was introduced by Fenton's reagent, 50% and 43% of which were then oxidized or demethylated to form As(V)/MMA (monomethyl arsenic), respectively. In the following drying process at 120-180 °C, the FeOOH and CaO derived by residual Fe/Ca conditioners could promote the oxidation of 30% of the rest As(III) by the catalytic effect or directly reacting with it. In the final steam gasification process, the very little As(III) left in the dry sludge was released with the gas phase and the proportion of As(V) in gasification ash almost reached 100%. In short, Fenton-CaO composite conditioning could achieve the near-zero emission of As and reduce the toxicity of the products throughout the whole sludge treatment process., (Copyright © 2022. Published by Elsevier Ltd.)

Due to its low molecular weight and abundant functional groups, water-soluble lignin (WSL) is considered as a more potent antioxidant than traditional industrial lignin in biofields. However, few studies have been conducted to evaluate its intracellular and endogenous reactive oxygen species (ROS)-scavenging ability, especially for the intervention of ROS-related disease in vivo. In this work, WSL in bamboo autohydrolysate (WSL-BM) and wheat stalk autohydrolysate (WSL-WS) were isolated and characterized to comparably analyze their bioactivities. The composition analysis and NMR characterization showed that both WSL-BM and WSL-WS contained relatively similar components and substructures, but WSL-BM contained higher contents of phenolic OH groups. Both WSL samples exhibited excellent biocompatibility with the concentration below 50 μg/mL, while WSL-BM exhibited superior ROS-scavenging ability and ROS-related ulcerative colitis treatment potential at same concentration. In addition, WSL-BM also showed better performance in ameliorating inflammation and oxidative stress in RAW 264.7 cells and colitis mice by activating Nrf2 and suppressing NFκB signaling, resulting in an overall improvement in both macroscopic and histological parameters. Overall, these results implied that WSL from gramineous biomass can be used as a novel anti-inflammatory and antioxidative agent in the biomedical field., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Due to the antioxidant properties of lignin, it has been demonstrated as an active substance for treating oxidation-related and inflammatory diseases. However, how the structural properties of lignin affect its biological activities is still ambiguous. In this study, Kraft lignin from wheat straw (KL-A) was used as the raw material to fractionate into three fractions (e.g., KL-B, KL-C, and KL-D) with different molecular weight by ultrafiltration, which possessed different physicochemical properties. The biocompatibility, in vivo and in vitro scavenging abilities for reactive oxygen species (ROS), and anti-apoptotic abilities of the lignin fractions were evaluated using SW1353 chondrocyte cell lines and were quantitatively fitted to their physicochemical properties. The results showed that lignin fractions with lower molecular weights, lower G/S ratios, and higher non-condensed phenolic OH contents endowed lignin with stronger ROS scavenging ability in vivo and in vitro, but was accompanied by increased cytotoxicity to cells. The half maximal inhibitory concentration (IC50) of KL-A, KL-B, KL-C, and KL-D were separately determined as 44.02, 33.43, 32.41, and 18.40 μg/mL. Furthermore, KL-D, with the lowest molecular weight and highest number of functional groups, showed the best antioxidant ability, while it performed poorly in inhibiting cellular apoptosis of chondrocytes. Compared to KL-D, KL-C with inverse structural properties, performed better in anti-apoptosis of SW1353 cells, which is the optimum lignin as promising active substances to be applied in the treatment of osteoarthritis in biomedical engineering., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The rapid diagnosis of tuberculosis (TB) is of great significance for the control and treatment of TB. However, TB remains a major healthy, social, and economic burden worldwide because of the lack of ideal diagnostic biomarkers. Mycobacterium tuberculosis (M. tuberculosis)- encoded small RNA (sRNA) is a class of regulation small RNA. Several studies have identified M. tuberculosis encoded-sRNAs in the serum/plasm of M. tuberculosis- infected patients. Small extracellular vesicles are small membrane vesicles secreted by many cell types during physiological and pathological conditions. Recent evidence has indicated that most of the nucleic acids in the serum/plasma are packaged in the small extracellular vesicles and could serve as ideal diagnostic biomarkers. In this study, we attempted a novel approach for TB diagnosis: targeting small extracellular vesicles M. tuberculosis encoded sRNA (sRNA) by qRT-PCR. The results showed that M. tuberculosis- encoded ASdes and MTB-miR5 only existed in tuberculosis patients and have the potential to serve as a sensitive and accurate methodology for TB diagnosis., 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 Lu, Jiang, Wu, Zhou, Liu, He, Zhang, Zen, Gu and Wang.)

Background: Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear., Results: Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity., Conclusions: In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.

Background: Paraquat is a widely used nonselective and fast-acting contact herbicide worldwide. This study identified the early predictor of mortality in patients with acute paraquat poisoning., Methods: Twenty-nine patients with acute paraquat poisoning admitted at Nanjing Drum Tower Hospital from January 2018 to August 2020 were included in this study. The early predictor of mortality in patients with acute paraquat poisoning based on the blood tests was identified by correlation, logistic regression, and receiver operating characteristic (ROC) analyses., Result: 15 of the 29 patients died after poisoning. Compared to the survivors, the neutrophilic granulocyte ratio, leukocyte count, ALB, and Crea of the nonsurvivors were significantly higher with p value < 0.05, while the lymphocyte ratio and eGFR(MDRD) of the nonsurvivors were remarkably lower with p value < 0.01. Moreover, the neutrophil-to-lymphocyte ratio (NLR) was remarkably upregulated in the nonsurvivors. The area under the ROC curve (AUC) of the neutrophilic granulocyte ratio, lymphocyte ratio, leukocyte count, ALB, Crea, eGFR(MDRD), and NLR to predict the mortality in patients with acute paraquat poisoning was 0.8905 (95% CI: 0.7589-1.022), 0.8643 (95% CI: 0.7244-1.004), 0.8500 (95% CI: 0.7133-0.9867), 0.7286 (95% CI: 0.5338-0.9233), 0.8167 (95% CI: 0.6620-0.9713), 0.8714 (95% CI: 0.7330-1.010), and 0.8667 (95% CI: 0.7277-1.006), respectively. More interestingly, we also evaluated the diagnostic values of the different combinations of six blood test biomarkers by logistic regression analysis. According to the results of the logistic regression analysis, the AUCs for the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) were the largest with 0.986 (95% CI: 0.952-1), and the sensitivity and specificity were 100% and 100%., Conclusion: This study demonstrated that the combination of the neutrophilic granulocyte ratio, leukocyte count, and eGFR(MDRD) could serve as an ideal early predictor of mortality in patients with acute paraquat poisoning. However, further research is needed to draw a clear conclusion., Competing Interests: The authors declare no potential conflicts of interest., (Copyright © 2020 Jun Wang et al.)

Tuberculosis (TB), one of the ancient and deadliest diseases, is a chronic immune disorder caused by Mycobacterium tuberculosis (Mtb) infection. Due to the lack of ideal diagnostic and therapeutic markers, TB is still posing a major health, social, and economic burden worldwide. Circular RNA (circRNA), a newly discovered endogenous RNA, is abundant and stable in the cytoplasm and has tissue specificity. More and more studies suggested circRNA is involved in a variety of human pathological and physiological processes. Recently, several studies have confirmed circRNAs not only existed in the serum but also could serve as ideal biomarkers for detecting diseases since the circRNAs have continuous, stable, and covalently closed circular structures and are not easily degraded by nucleases. In this study, we screened the circRNA expression profiles in active TB serum samples and healthy volunteers serum samples by circRNA microarrays. Then, we performed qRT-PCR to verified the dysregulated circRNAs and ROC curve analysis to evaluate the value of circRNAs for TB diagnosis. The results showed circRNA&#95;051239, circRNA&#95;029965, and circRNA&#95;404022 could serve as biomarkers for TB diagnosis., (Copyright © 2020 Liu, Lu, Wang, Jiang, Gu, Wang, Yan, He and Wang.)

Background: The thermo-sensitive genic male sterility (TGMS) of Brassica napus facilitates reproductive researches and hybrid seed production. Considering the complexity and little information about the molecular mechanism involved in B. napus TGMS, comparative transcriptomic analyses were peroformed for the sterile (160S-MS) and fertile (160S-MF) flowers to identify potential crucial genes and pathways associated with TGMS., Results: In total, RNA-seq analysis showed that 2202 genes (561 up-regulated and 1641 down-regulated) were significantly differentially expressed in the fertile flowers of 160S-MF at 25 °C when compared the sterile flower of 160S-MS at 15 °C. Detailed analysis revealed that expression changes in genes encoding heat shock proteins, antioxidant, skeleton protein, GTPase and calmodulin might be involved in TGMS of B. napus. Moreover, gene expression of some key members in plant hormone signaling pathways, such as auxin, gibberellins, jasmonic acid, abscisic acid, brassinosteroid signalings, were significantly surppressed in the flowers of 160S, suggesting that these genes might be involved in the regulation in B. napus TGMS. Here, we also found that transcription factor MADS, NFY, HSF, MYB/C and WRKY might play a crucial role in male fertility under the high temperature condition., Conclusion: High temperature can significant affect gene expression in the flowers. The findings in the current study improve our understanding of B. napus TGMS at the molecular level and also provide an effective foundation for male fertility researches in other important economic crops.

Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). Increasing evidence has demonstrated that the inflammatory response triggers demyelination and gliosis in demyelinating disorders. Numerous clinical interventions, including those used to treat multiple sclerosis (MS), have confirmed prednisone (PDN) as a powerful anti-inflammatory drug that reduces the inflammatory response and promotes tissue repair in multiple inflammation sites. However, the underlying mechanism of PDN in ameliorating myelin damage is not well understood. In our study, a cuprizone (CPZ)-induced demyelinated mouse model was used to explore the mechanism of the protection provided by PDN. Open-field tests showed that CPZ-treated mice exhibited significantly increased anxiety and decreased exploration. However, PDN improved emotional behavior, as evidenced by an increase in the total distance traveled, and central distance traveled as well as the mean amount of time spent in the central area. CPZ-induced demyelination was observed to be alleviated in PDN-treated mice based on luxol fast blue (LFB) staining and myelin basic protein (MBP) expression analyses. In addition, PDN reduced astrocyte and microglia activation in the corpus callosum. Furthermore, we demonstrated that PDN inhibited the Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathway and related inflammatory cytokines and chemokines, including TNF-α, CCL8, CXCL10 and CXCL16. PDN also reduced the serum corticosterone levels in the CPZ-treated mice. Taken together, these results suggest that inhibition of the NLRP3 signaling pathway may be a novel mechanism by which PDN exerts its protective actions in demyelinating diseases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Doppler wind Lidar is an important method for atmospheric wind measurement. The Doppler frequency shift of backscattering spectrum due to the wind is detected from the transmissions of frequency discrimination. High sensitivity and large dynamic range measurement is difficult for atmospheric wind measurement because of the limitationof frequency discriminator characteristic. In this paper, a frequency discriminator constructed with Dual fiber Mach-Zehnder interferometer is proposed. Two fiber Mach-Zehnder interferometers with different atmospheric wind detection dynamic range and sensitivity are designed and used to measure Doppler frequency shift at the same time. The optical path difference of FMZI-2 is 13.7 cm which can realize large dynamic range wind measurement (±100 m·s-1) and the optical path difference of FMZI-1is designed to be 74.8 cm which can realize high sensitivity detection. Moreover, the absolute wind velocity of FMZI-1 channel can be corrected by the measurement result of FMZI-2 channel. Thus the high sensitivity and large dynamic range wind detection can be realized. The sensitivity, SNR and wind error of two channels are simulated and analyzed for different parameters. The results indicate that the system can realize the wind error less than 1 m·s-1 for large dynamic range(±100 m·s-1) wind velocity, which is a beneficial exploration for high sensitivity and large dynamic range Doppler wind lidar.

To establish a method for the identification of five species and one variety of medicinal plants from Diospyros, their leaf veins, epidermis, anatomic and powder characters were observed and compared with macro-morphological and microscopic methods. The results indicated the differences of secondary and tertiary veins among those Diospyros species. The single cell non-glandular hair and glandular hair exist in most species' epidermis while stone cells were only found in the leaf powders of two species. Through the study, the main differences of leaf macro- and micro-morphology of these species were obtained and practical keys were also established, which can provide scientific base not only for identification of these species during their vegetative stages, but also for accuracy authentication of the source of Kaki Folium., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Easy-to-use dipstick tests for lead have been developed by immobilizing nanoparticle-DNAzyme conjugates on lateral flow devices and their application for detecting lead in paints is demonstrated.