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Lipopolysaccharides (LPS) is the major compoent of Gram-negative bacteria and an important factor in inducing inflammation, which usually leads to multiple organ failure in broilers, seriously affecting the growth performance of broilers and hindering the development of poultry farming. Under the policy of prohibiting antibiotics in feed, it has become more urgent to find natural drugs to prevent liver damage caused by LPS in broilers. Asiatic acid (AA) is a pentacyclic triterpene that has been proven to have anti-inflammatory and antioxidant effects. However, the protective effects of AA in LPS-induced liver damage in broilers still need to be clarified. This study aims to explore the complete mechanism of AA against LPS-induced acute liver injury (ALI) in broilers. A total of 60 broilers (1 day old) were randomly divided into the control group, LPS group, LPS+AA (15, 30 and 60 mg/kg) group and control+AA (60 mg/kg) group. At 16, 18 and 20 days of age, the broilers were attacked with LPS (0.5 mg/kg) to construct liver injury model. H&E staining assessed liver pathological changes. The mRNA and protein expression levels related to the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis in the liver tissue were detected. Our results founded that intraperitoneal injection of LPS in broilers increased the activities of AST and ALT, as well as raising the related gene and protein expression of the HMGB1/TLR4/NF-κB pathway, pyroptosis, and ERS-mediated apoptosis. Interestingly, AA improved LPS-induced liver damage and decreased the activities of AST and ALT in broilers. Additionally, AA mitigated LPS-induced ALI by reducing the mRNA levels and protein expressions of the HMGB1/TLR4/NF-κB pathway, pyroptosis and ERS-mediated apoptosis. In conclusion, the present study investigated that AA mitigated LPS-induced ALI in broilers by reducing pyroptosis and ERS-mediated apoptosis via inhibition of the HMGB1/TLR4/NF-κB pathway. Therefore, AA may serve as a potential feed additive for the prevention of LPS-induced ALI in broilers., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: The Chronic Lymphocytic Leukemia (CLL) treatment strategies have transitioned from chemotherapy and chemoimmunotherapy to chemo-free regimens. Frequentist network meta-analysis allows for both direct and indirect comparisons between different treatments., Methods: Randomized controlled trials assessing first-line treatments were included. Outcomes were progression-free survival (PFS), overall survival, undetectable minimal residual disease (MRD), objective response rate, and adverse events. Studies with comparable characteristics also underwent subgroup analysis, stratifying by age, comorbidities, IGHV status, and cytogenetic abnormalities., Results: 30 eligible trials involved 12,818 patients and 30 treatments were included. Acalabrutinib demonstrated a PFS advantage over ibrutinib and obinutuzumab-venetoclax (OV) in patients over 65 years old or with unmutated IGHV. In younger patients with comorbidities, Acalabrutinib-Obinutuzumab (AO) had superior PFS compared to Ibrutinib-Obinutuzumab (IO), Ibrutinib-Venetoclax (IV), and OV. For older patients with comorbidities, Acalabrutinib and AO both outperformed OV without significant difference between them. MRD-guided IV surpassed OV in patients without comorbidities. IO exhibited extended PFS benefits compared to OV in patients with mutated IGHV or with del(17p) and/or TP53 mutations. IV and IO have lower neutropenia rates than OV. IV have fewer infections than Acalabrutinib and AO. AO causes less diarrhea than IV but more headaches than IO and OV. OV has lower hypertension rates than IO. IV has fewer arthralgia than AO. For any grade secondary primary neoplasms, IV and OV is less than AO., Conclusion: Tailored chemo-free regimens can be selected based on age, comorbidities, IGHV status, and cytogenetic abnormalities to optimize treatment outcomes while considering different response spectra., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: This study aimed to elucidate the alterations in Follistatin-like protein 1 (FSTL1) and its association with the pathological process of periodontitis., Methods: This study included 48 patients with periodontitis and 42 healthy controls. The expression level of FSTL1 in the gingiva was determined by RT-qPCR, validated using the dataset GSE16134, and subsequently examined by western blotting. Bioinformatics analysis revealed a single-cell distribution of FSTL1, characteristic of angiogenesis and immune cell infiltration. The expression and distribution of FSTL1, vascular endothelial marker protein CD31 and myeloperoxidase (MPO), the indicator of neutrophil activity, were determined by immunohistochemistry (IHC). A series of correlation analyses was performed to determine the associations between FSTL1 and clinical parameters, including probing depth (PD) and clinical attachment loss (CAL), and their potential role in angiogenesis (CD31) and neutrophil infiltration (MPO)., Results: FSTL1 was significantly upregulated in the gingiva of patients with periodontitis compared to their healthy counterparts. In addition, FSTL1 was positively correlated with the clinical parameters PD (r = .5971, p = .0005) and CAL (r = .6078, p = .0004). Bioinformatic analysis and IHC indicated that high FSTL1 expression was significantly correlated with angiogenesis and neutrophil infiltration in periodontitis. Moreover, receiver operating characteristic (ROC) analysis demonstrated that FSTL1 could serve as an independent indicator for evaluating the severity of periodontitis (area under the curve [AUC] = 0.9011, p < .0001)., Conclusion: This study demonstrated FSTL1 upregulation in periodontitis and its potential contribution to the disease via angiogenesis and neutrophil infiltration., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Soil salinity pollution is increasing worldwide, seriously affecting plant growth and crop production. Existing reports on how potassium indole-3-butyric acid (IBAK) regulates rice salt stress adaptation by affecting rice carbon metabolism, transcription factor (TF) genes expression, and biosynthesis of secondary metabolites still have limitations. In this study, an IBAK solution at 40 mg L -1 was sprayed on rice leaves at the seedling stage. The results showed that the IBAK application could promote shoot and root growth, decrease sucrose and fructose content, increase starch content, and enhance acid invertase (AI) and neutral invertase (NI) activity under salt stress, indicating altered carbon allocation. Furthermore, the expression of TF genes belonging to the ethylene responsive factor (ERF), WRKY, and basic helix-loop-helix (bHLH) families was influenced by IBAK. Many key genes ( OsSSIIc , OsSHM1 , and OsPPDKB ) and metabolites (2-oxoglutaric acid, fumaric acid, and succinic acid) were upregulated in the carbon metabolism pathway. In addition, this study highlighted the role of IBAK in regulating the biosynthesis of secondary metabolites pathway, potentially contributing to rice stress adaptability. The results of this study can provide new sustainable development solutions for agricultural production., 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 Zhou, Meng, Jiang, Lu, Zhang, Huang, Wu, Deng, Wang, Zhao, Du, Huo, Du, Feng and Zheng.)

Hypervascularized glioblastoma is naturally sensitive to anti-angiogenesis but suffers from low efficacy of transient vasculature normalization. In this study, a lipid-polymer nanoparticle is synthesized to execute compartmentalized Cas9 and sgRNA delivery for a permanent vasculature editing strategy by knocking out the signal transducer and activator of transcription 3 (STAT3). The phenylboronic acid branched cationic polymer is designed to condense sgRNA electrostatically (inner compartment) and patch Cas9 coordinatively (outer compartment), followed by liposomal hybridization with angiopep-2 decoration for blood-brain barrier (BBB) penetration. The lipid-polymer nanoparticles can reach glioblastoma within 2 h post intravenous administration, and hypoxia in tumor cells triggers charge-elimination and degradation of the cationic polymer for burst release of Cas9 and sgRNA, accompanied by instant Cas9 RNP assembly, yielding ≈50% STAT3 knockout. The downregulation of downstream vascular endothelial growth factor (VEGF) reprograms vasculature normalization to improve immune infiltration, collaborating with interleukin-6 (IL-6) and interleukin-10 (IL-10) reduction to develop anti-glioblastoma responses. Collectively, the combinational assembly for compartmentalized Cas9/sgRNA delivery provides a potential solution in glioblastoma therapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The degradation of sodium alginate by human gut microbiota was found to be retarded via calcium cross-linking in our previous study. We hypothesized that the guluronic acid block (GB) on the alginate molecule might be the key structural region affecting alginate degradation by the gut microbiota when cross-linked with calcium. This study aims to prove this hypothesis by studying the structural features of the cross-linked GB on its in vitro fecal fermentation behaviors concerning the aspects of total carbohydrate contents, monosaccharide contents, short-chain fatty acids production, calcium state variations, and structural variations. Herein, GB isolated from sodium alginate was cross-linked under ranges of molar ratios of [Ca 2+ ]/[-COOH] that further restricted the degradation by gut microbiota similar to the cross-linked alginates. First, total carbohydrate contents, short-chain fatty acids production, monosaccharides contents, and calcium state analyses confirmed that the degradation of GB by gut microbiota was restricted by calcium cross-linking. Furthermore, the tracking analysis of structural variations during in vitro fermentation revealed that the "granules" structure could further restrict degradation by the gut microbiota, leaving more cross-linked GB fragments surviving in comparison to the "networks" structure. In addition, Bacteroides xylanisolvens showed a significant positive correlation to the "cross-linking porosity ( R = 0.825, p < 0.001), which supported our previous findings on fermentation behaviors of cross-linked alginate. Together, guluronic acid blocks are the key structural regions that retard the degradation of sodium alginate by the gut microbiota when cross-linked with calcium.

Background: Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the molecular mechanism of macrophages in pre-eclampsia is not well understood., Methods: In this study, the key biomarkers during the development of pre-eclampsia were identified using bioinformatics analysis. The GSE75010 and GSE74341 datasets from the GEO database were obtained and merged for differential analysis. A weighted gene co-expression network analysis (WGCNA) was constructed based on macrophage content, and machine learning methods were employed to identify key genes. Immunoinfiltration analysis completed by the CIBERSORT method, R package "ClusterProfiler" to explore functional enrichment of these intersection genes, and potential drug predictions were conducted using the CMap database. Lastly, independent analysis of protein levels, localization, and quantitative analysis was performed on placental tissues collected from both preeclampsia patients and healthy control groups., Results: We identified 70 differentially expressed NETs genes and found 367 macrophage-related genes through WGCNA analysis. Machine learning identified three key genes: FNBP1L, NMUR1, and PP14571. These three key genes were significantly associated with immune cell content and enriched in multiple signaling pathways. Specifically, these genes were upregulated in PE patients. These findings establish the expression patterns of three key genes associated with M2 macrophage infiltration, providing potential targets for understanding the pathogenesis and treatment of PE. Additionally, CMap results suggested four potential drugs, including Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin, which may have the potential to reverse pre-eclampsia., Conclusion: Studying the expression levels of three key genes in pre-eclampsia provides valuable insights into the prevention and treatment of this condition. We propose that these genes play a crucial role in regulating the maternal-fetal immune microenvironment in PE patients, and the pathways associated with these genes offer potential avenues for exploring the molecular mechanisms underlying preeclampsia and identifying therapeutic targets. Additionally, by utilizing the Connectivity Map database, we identified drug targets like Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin as potential clinical treatments for preeclampsia., 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 Cao, Jiang, Yin, Li, Tong and Qi.)

Salt stress is one of the major abiotic stresses that damage the structure and composition of cell walls. Alginate oligosaccharides (AOS) have been advocated to significantly improve plant stress tolerance. The metabolic mechanism by which AOS induces salt tolerance in rice cell walls remains unclear. Here, we report the impact of AOS foliar application on the cell wall composition of rice seedlings using the salt-tolerant rice variety FL478 and the salt-sensitive variety IR29. Data revealed that salt stress decreased biomass, stem basal width, stem breaking strength, and lodging resistance; however, it increased cell wall thickness. In leaves, exogenous AOS up-regulated the expression level of OSCESA8 , increased abscisic acid (ABA) and brassinosteroids (BR) content, and increased β-galacturonic activity, polygalacturonase activity, xylanase activity, laccase activity, biomass, and cellulose content. Moreover, AOS down-regulated the expression levels of OSMYB46 and OSIRX10 and decreased cell wall hemicellulose, pectin, and lignin content to maintain cell wall stability under salt stress. In stems, AOS increased phenylalamine ammonia-lyase and tyrosine ammonia-lyase activities, while decreasing cellulase, laccase, and β-glucanase activities. Furthermore, AOS improved the biomass and stem basal width and also enhanced the cellulose, pectin, and lignin content of the stem, As a result, increased resistance to stem breakage strength and alleviated salt stress-induced damage, thus enhancing the lodging resistance. Under salt stress, AOS regulates phytohormones and modifies cellulose, hemicellulose, lignin, and pectin metabolism to maintain cell wall structure and improve stem resistance to lodging. This study aims to alleviate salt stress damage to rice cell walls, enhance resistance to lodging, and improve salt tolerance in rice by exogenous application of AOS.

In order to explore the regulating role and the physiological and biochemical mechanisms of trans-abscisic acid (hereinafter referred as S-ABA) in the process of rice growth and development under salt stress, we took Chaoyou 1000 and Yuxiangyouzhan as materials and set up three salt concentration treatments, CK0 (Control treatment), N1 (50 mmol L -1 NaCl), and N2 (100 mmol L -1 NaCl), in potted trials; we aimed to study the mechanism of rice's response to salt stress from the perspective of agricultural traits and physiological biochemicals and to improve rice's resistance to salt stress through exogenously applying the regulating technology of S-ABA. The following results were obtained: Under salt stress, the growth of rice was significantly suppressed compared to CK0, exhibiting notable increases in agricultural indicators, photosynthesis efficiency, and the NA + content of leaves. However, we noted a significant decrease in the K + content in the leaves, alongside a prominent increase in NA + /K + and a big increase in MDA (malondialdehyde), H 2 O 2 (hydrogen peroxide), and O 2 - (superoxide anion). This caused the cytomembrane permeability to deteriorate. By applying S-ABA under salt stress (in comparison with salt treatment), we promoted improvements in agronomic traits, enhanced photosynthesis, reduced the accumulation of NA + in leaves, increased the K + content and the activity of antioxidant enzymes, and reduced the active oxygen content, resulting in a sharp decrease in the impact of salt stress on rice's development. The application of S-ABA decreased the endogenous ABA (abscisic acid) content under salt stress treatment but increased the endogenous GA (gibberellin) and IAA (indole acetic acid) contents and maintained the hormonal homeostasis in rice plants. To summarize, salt stress causes damage to rice growth, and the exogenous application of S-ABA can activate the pouring system mechanism of rice, suppress the outbreak of active oxygen, and regulate NA + /K + balance and hormone homeostasis in the blades, thus relieving the salt stress.

The aim of this experiment was to investigate the effects of exogenous sprays of 5-aminolevulinic acid (5-ALA) and 2-Diethylaminoethyl hexanoate (DTA-6) on the growth and salt tolerance of rice ( Oryza sativa L.) seedlings. This study was conducted in a solar greenhouse at Guangdong Ocean University, where 'Huanghuazhan' was selected as the test material, and 40 mg/L 5-ALA and 30 mg/L DTA-6 were applied as foliar sprays at the three-leaf-one-heart stage of rice, followed by treatment with 0.3% NaCl (W/W) 24 h later. A total of six treatments were set up as follows: (1) CK: control, (2) A: 40 mg⋅ L -1 5-ALA, (3) D: 30 mg⋅ L -1 DTA-6, (4) S: 0.3% NaCl, (5) AS: 40 mg⋅ L -1 5-ALA + 0.3% NaCl, and (6) DS: 30 mg⋅ L -1 DTA-6+0.3% NaCl. Samples were taken at 1, 4, 7, 10, and 13 d after NaCl treatment to determine the morphology and physiological and biochemical indices of rice roots. The results showed that NaCl stress significantly inhibited rice growth; disrupted the antioxidant system; increased the rates of malondialdehyde, hydrogen peroxide, and superoxide anion production; and affected the content of related hormones. Malondialdehyde content, hydrogen peroxide content, and superoxide anion production rate significantly increased from 12.57% to 21.82%, 18.12% to 63.10%, and 7.17% to 56.20%, respectively, in the S treatment group compared to the CK group. Under salt stress, foliar sprays of both 5-ALA and DTA-6 increased antioxidant enzyme activities and osmoregulatory substance content; expanded non-enzymatic antioxidant AsA and GSH content; reduced reactive oxygen species (ROS) accumulation; lowered malondialdehyde content; increased endogenous hormones GA3, JA, IAA, SA, and ZR content; and lowered ABA content in the rice root system. The MDA, H 2 O 2 , and O 2- contents were reduced from 35.64% to 56.92%, 22.30% to 53.47%, and 7.06% to 20.01%, respectively, in the AS treatment group compared with the S treatment group. In the DS treatment group, the MDA, H 2 O 2 , and O 2- contents were reduced from 24.60% to 51.09%, 12.14% to 59.05%, and 12.70% to 45.20%. In summary, NaCl stress exerted an inhibitory effect on the rice root system, both foliar sprays of 5-ALA and DTA-6 alleviated damage from NaCl stress on the rice root system, and the effect of 5-ALA was better than that of DTA-6., Competing Interests: The authors declare there are no competing interests., (©2024 Wang et al.)

A large number of dead seedlings can occur in saline soils, which seriously affects the large-scale cultivation of rice. This study investigated the effects of plant growth regulators (PGRs) and nitrogen application on seedling growth and salt tolerance ( Oryza sativa L.), which is of great significance for agricultural production practices. A conventional rice variety, "Huang Huazhan", was selected for this study. Non-salt stress treatments included 0% NaCl (CK treatment), CK + 0.05 g N/pot (N treatment), CK + 40 mg·L -1 5-aminolevulinic acid (5-ALA) (A treatment), and CK + 30 mg·L -1 diethylaminoethyl acetate (DTA-6) (D treatment). Salt stress treatments included 0.3% NaCl (S treatment), N + 0.3% NaCl (NS treatment), A + 0.3% NaCl (AS treatment), and D + 0.3% NaCl (DS treatment). When 3 leaves and 1 heart emerged from the soil, plants were sprayed with DTA-6 and 5-ALA, followed by the application of 0.3% NaCl ( w / w ) to the soil after 24 h. Seedling morphology and photosynthetic indices, as well as carbohydrate metabolism and key enzyme activities, were determined for each treatment. Our results showed that N, A, and D treatments promoted seedling growth, photosynthesis, carbohydrate levels, and the activities of key enzymes involved in carbon metabolism when compared to the CK treatment. The A treatment had the most significant effect, with increases in aboveground dry weight and net photosynthetic rates (Pn) ranging from 17.74% to 41.02% and 3.61% to 32.60%, respectively. Stomatal limiting values (Ls) significantly decreased from 19.17% to 43.02%. Salt stress significantly inhibited seedling growth. NS, AS, and DS treatments alleviated the morphological and physiological damage of salt stress on seedlings when compared to the S treatment. The AS treatment was the most effective in improving seedling morphology, promoting photosynthesis, increasing carbohydrate levels, and key enzyme activities. After AS treatment, increases in aboveground dry weight, net photosynthetic rate, soluble sugar content, total sucrose synthase, and amylase activities were 17.50% to 50.79%, 11.39% to 98.10%, 20.20% to 80.85%, 21.21% to 33.53%, and 22.17% to 34.19%, respectively, when compared to the S treatment. In summary, foliar sprays of 5-ALA, DTA-6, and additional nitrogen fertilizer enhanced rice seedling growth, increased photosynthesis, lowered Ls values, and improved seedling salt tolerance. Spraying two regulators, 5-ALA and DTA-6, quantitatively increased the effect of nitrogen fertilizer, with comparable effects on NaCl stress regulation. This study provides the basis for efficient agricultural production.

Single-cell multiplexed phenotypic analysis expands the biomarkers for diagnosis, heralding a new era of precision medicine. Cell secretions are the primary measures of immune function, but single-cell screening remains challenging. Here, a novel cell membrane-based assay was developed using cholesterol-linked antibodies (CLAbs), integrating immunosorbent assays and droplet microfluidics to develop a flexible high-throughput single-cell secretion assay for multiplexed phenotyping. CLAb-grafted single cells were encapsulated in water-in-oil droplets to capture their own secretions. Subsequently, the cells were extracted from droplets for fluorescence labeling and screening. Multiple secretions and surface proteins were simultaneously measured from single cells by flow cytometry. To validate the approach, THP-1 cells, THP-1-derived M1 macrophages, and dendritic cells were assayed, indicating the differentiation efficiency of THP-1 cells under different chemical stimulations. Moreover, peripheral blood mononuclear cells from healthy donors under various stimuli showed varied active immune cell populations (6.62-47.14%). The peripheral blood mononuclear cells (PBMCs) of nasopharyngeal carcinoma patients were analyzed to identify a higher percentage of actively cytokine-secreted single cells in the basal state (2.82 ± 1.48%), compared with that in the health donors (0.70 ± 0.29%).

Hexadecyltrimethylammonium bromide complexed alginate-Ca 2+ microgels (C/AMGs) were developed as emulsifiers, which shown remarkably improved emulsifying performance than non-complexed alginate-Ca 2+ microgels (AMGs) in previous study. This work focus on the impact of deformability on the emulsifying performance of C/AMGs. By regulating alginate concentration (1.0-4.0 wt%), microgels with different deformability were prepared. Deformability was proved to have great influence on the emulsifying performance of C/AMGs, which was evaluated by Langmuir trough measurements, emulsion appearance, centrifugation stability, digestive behavior, and oxidative stability. Particle size and SEM images indicated microgels prepared with lower alginate concentration are more deformable. C/AMGs (2.0 wt%) exhibits the best emulsifying performance, which could be ascribed to the appreciated deformability and mechanical strength. Digestive behavior and oxidative stability of alginate-Ca 2+ microgel (2.0 wt%) stabilized emulsions were further investigated. Compared with alginate-Ca 2+ microgel (2.0 wt%) stabilized emulsions, C/AMGs (2.0 wt%) stabilized emulsions shown delayed lipid digestion and lower POV. Results of this work supporting that Mickering mechanism have potential in fabricating functional emulsions based on natural polysaccharides., 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. Published by Elsevier B.V.)

Background: Hearing loss can exacerbate cognitive decline; therefore, exploring the mechanisms through which hearing loss affects cognitive function is crucial. The current study aimed to investigate the impact of hearing loss on cognitive function and the mediating role played by self-rated health and depressive anxiety symptoms., Methods: Using stratified whole-group random sampling, the study employed a cross-sectional design and included 624 participants aged ≥65 years from three communities in Urumqi, China. Cognitive function was assessed using the Mini-Mental State Examination. Hearing function and self-rated health were determined by self-report. The 15-item Geriatric Depression Scale and the 7-item Generalized Anxiety Disorder Scale were used to assess depressive anxiety symptoms. Serial mediation analysis was performed using AMOS 26.0., Results: Hearing loss can not only negatively affect cognitive function in older adults directly (direct effect = -0.106; SE = 0.045; 95% confidence interval (CI): -0.201 to -0.016), but also indirectly affect the relationship between hearing loss and cognitive function through self-rated health and depressive anxiety symptoms. The results of the serial mediation analysis showed that the total indirect effect of self-rated health and depressive anxiety symptoms was -0.115 (95% CI: -0.168 to -0.070), and the total effect of the model was -0.221 (95% CI: -0.307 to -0.132), with the total indirect effect accounting for 52.04% of the total effect of the model., Conclusion: Our study discovered that there is a partial mediation of the relationship between hearing loss and cognitive function by self-rated health and depressive anxiety symptoms. It is suggested that by enhancing self-rated health and ensuring good mental health, the decline in cognitive function among older adults with hearing loss can be delayed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Chen, Jiang, Li, Ning, Hu, Jiang, Zhang, Feng and Yan.)

Free amino acids (FAAs) are believed to play important roles in osmoregulation and buffer capacity in some aquatic animals, such as fishes. However, the potential roles of FAAs have not been systematically summarized and characterized until now. In the present study, the meta-analysis was conducted to investigate the relationships between FAAs and environmental salinities. Twenty published documents were included, accounting for 106 study cases. The effect sizes of total free amino acids (TFAAs), total essential amino acids (TEAAs), and total non-essential amino acids (TNEAAs) to salinity increase were calculated and determined by the restricted maximum likelihood (REML) method. It clearly showed that the elevated salinities significantly induced the contents of TFAAs, TEAAs, and TNEAAs at the ratio of 36%, 27%, and 29%, respectively. Faced to the salinity changes, the contents of FAAs in fishes under freshwater and seawater varied significantly, while the individuals under brackish water displayed relatively constant contents of FAAs. When salinity elevated, the contents of 17 amino acids in muscles significantly increased, suggesting the important roles of FAA metabolism in osmoregulation in fishes. The results also indicated that the effect sizes of TFAAs were positively related to the rates of salinity increases, and exhibited a significant quadratic linear relationship with temperatures. Additionally, the contents of FAAs also showed positive correlation with osmotic pressure, concentrations of plasma Na + , Cl - , and urea, implying their potential roles of FAAs in osmoregulation in fishes. These findings suggested that elevated salinities greatly induced the contents of FAAs in fishes, making a great contribution to maintaining the homeostasis of fishes in response to environmental salinity changes., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Agarose microgels were prepared with bottom-up approach, and emulsifying properties of agarose microgels were investigated. Physical properties of microgels are varied with agarose concentration, and further affect the emulsifying performance of microgels. Enhanced surface hydrophobicity index and decreased particle size of microgels were recorded with the increasing of agarose concentration, which were conducive to emulsifying properties of microgels. Improved interfacial adsorption of microgels was evidenced by Dynamic surface tension and SEM. However, microscopic morphology of microgel at O/W interface indicated that increasing agarose concentration could weaken the deformability of microgels. The influence of external conditions (pH and NaCl) on the physical properties of microgels were investigated, and their effects on emulsion stability were evaluated. Compared with acidification, NaCl was appeared to be more destructive to emulsion stability. Results indicated acidification and NaCl could decrease surface hydrophobicity index of microgels, but there was differentiation in the variation of particle size. It was inferred that deformability of microgels could make contribution to the stability of emulsion. This study verified that microgelation was a feasible scheme to improve the interfacial properties of agarose, and the influence of agarose concentration, pH, and NaCl on the emulsifying performance of microgels was investigated., 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.)

Objective: To evaluate the effect of butylphthalide combined with oxiracetam on cognitive function, intellectual recovery and serum inflammatory factors in patients with cognitive impairment after cerebral infarction., Methods: This is a Clinical comparative study. A total of 80 patients with cognitive impairment after cerebral infarction who visited Renmin Hospital, Hubei University of Medicine from January 2020 to January 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with oral oxiracetam combined with routine treatment. Patients in the study group were given butylphthalide combined with oxiracetam on the basis of routine treatment. Compare the clinical effect, cognitive function and intellectual recovery, inflammatory factor level changes, CBV, CBF, MTT and other cerebral blood flow perfusion indicators, as well as post-treatment incidence of adverse drug reactions in the two groups of patients., Results: The efficacy of the study group was significantly higher than that of the control group (p=0.03). After treatment, the levels of CBV and CBF in the study group were higher than those in the control group, the levels of TNF-α, CRP and IL-6 were significantly lower than those of the control group, while MTT was shorter than that in the control group, with statistically significant difference (p=0.00). Furthermore, there was a statistically significant difference that the MMSE score and MOCA score of the study group were higher than those of the control group (p=0.00)., Conclusion: Butylphthalide combined with oxiracetam has an obvious curative effect in the treatment of patients with cognitive impairment after cerebral infarction. It is a safe and effective therapeutic option that can significantly recover cognitive function and intelligence, improve cerebral blood flow perfusion and reduce inflammatory factors, without an obvious increase in adverse reactions., (Copyright: © Pakistan Journal of Medical Sciences.)

The aim of the study was to describe an approach where condylar resection with condylar neck preservation was combined with Le Fort I osteotomy and unilateral mandibular sagittal split ramus osteotomy (SSRO). Patients with a unilateral condylar osteochondroma combined with dentofacial deformity and facial asymmetry who underwent surgery between January 2020 and December 2020 were enrolled. The operation included condylar resection, Le Fort I osteotomy and contralateral mandibular sagittal split ramus osteotomy (SSRO). Simplant Pro 11.04 software was used to reconstruct and measure the preoperative and postoperative craniomaxillofacial CT images. The deviation and rotation of the mandible, change in the occlusal plane, position of the "new condyle" and facial symmetry were compared and evaluated during follow-up. Three patients were included in the present study. The patients were followed up for 9.6 months on average (range, 8-12). Immediate postoperative CT images showed that the mandible deviation and rotation and occlusion plane canting decreased significantly postoperatively; facial symmetry was improved but still compromised. During the follow-up, the mandible gradually rotated to the affected side, the position of the "new condyle" moved further inside toward the fossa, and both the mandible rotation and facial symmetry were more significantly improved. Within the limitations of the study it seems that for some patients a combination of condylectomy with condylar neck preservation and unilateral mandibular SSRO can be effective in achieving facial symmetry., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Whether immunotherapy combined with different histone deacetylases (HDAC) inhibitors in refractory or relapsed natural killer/T-cell lymphoma (NKTCL) is superior to each agent is still lacking in head-to-head clinical trials or preclinical evidence., Methods: NKTCL cell line xenograft models (CDX) in immunocompetent, human programmed cell death protein 1 (PD1) knock-in genetically engineered mice were used to investigate the combination effects. Different types and dosages of HDAC inhibitors were investigated. We explored the underlying mechanisms by RNA-sequencing and ChIP-sequencing. Two clinical cases treated with anti-PD1/chidamide were presented., Findings: Anti-PD1/chidamide shows significant tumour rejection in two CDX models. RNA-seq and CHIP-seq revealed that chidamide is synergistic to enhance T-cell chemokine expression, augment the Ifn-γ response, and increase CD8 T-cell infiltration via histone modification. Ifn-γ neutralizing antibody can attenuate the efficacy of combination drugs. However, the anti-PD1/romidepsin failed to augment the Ifn-γ response. The expressions of Ifn-γ related gene set signatures are significantly correlated with tumour rejection in anti-PD1/chidamide. In the clinic, two NKTCL patients treated with the PD1/chidamide show promising efficacy and limited toxicity., Interpretation: Anti-PD1/chidamide enhances T-cell chemokine expression and augments the IFN-γ response in preclinical NKTCL immunocompetent models. IFN-γ signatures may be good response biomarkers for the selection of potentially benefit patients., Funding: This study was supported by the Chinese National Major Project for New Drug Innovation (2017ZX09304015) and the Chinese Society of Clinical Oncology Research Fund (Y-BMS2019-026)., Competing Interests: Declaration of interests The authors declare no potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: This study aims to explore the therapeutic effects of bevacizumab combined with oxaliplatin on patients with malignant pleural effusion of lung cancer., Methods: A total of 109 patients with malignant pleural effusion of lung cancer admitted to our hospital from March 2015 to April 2017 were selected as research objects. Among them, 59 patients treated with bevacizumab combined with oxaliplatin intrathoracic injection were enrolled in the observation group, and another 50 patients treated with oxaliplatin intrathoracic injection were enrolled in the regular group. Clinical efficacy and safety of the two groups were compared, as well as the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR) and tumor markers before and after treatment. The two groups of patients were followed up for 3 years to compare their prognosis, survival and quality of life., Results: The cure rate of the observation group was higher than that of the regular group ( P < 0.05), but there was no difference in the incidence of adverse reactions ( P > 0.05). After treatment, VEGF, VEGFR and tumor markers in the observation group were significantly lower than those in the regular group ( P < 0.05), while the survival rate and quality of life of the observation group were significantly higher than those in the regular group ( P < 0.05)., Conclusion: Bevacizumab combined with oxaliplatin intrathoracic injection is effective in treating malignant pleural effusion of lung cancer., Competing Interests: None., (AJTR Copyright © 2021.)

Objective: This study investigated the role and mechanism of calcineurin (CaN)-nuclear factor of activated T cells (NFAT) pathway in the myoblast apoptosis induced by cyclic tensile strain., Methods: Myoblasts were cultured using an in vitro-mechanical stimulation model and imposed with tension for different hours with a multi-channel cell stress loading system. Cyclosporine (CsA) was used as CaN inhibitor to clarify the role of CaN in the apoptosis induced by cyclic stress. Hochest 33258 staining and flow cytometry detection were performed to detect the apoptotic cells. Real-time polymerase chain reaction was conducted to detect the mRNA expression of CaN and NFAT. Protein levels of NFAT3 were evaluated by Western blot., Results: The apoptosis rate increased with the extension of loading time. The mRNA expression of the CaN subunits, CnA and CnB, and the protein levels of NFAT3 also increased. When the myoblasts were incubated with CsA, the apoptosis rate decreased, the mRNA expression of CnA and NFAT3 significantly decreased, and the NFAT3 protein expression levels became significantly lower than those of the groups without CsA., Conclusion: Continuous cyclic tensile stress can induce myoblast apoptosis. The CaN-NFAT signaling pathway may be involved in the cyclic stretch-induced apoptosis of myoblasts.

Objective: To investigate the predominant contribution of methyl-metabolism pathway to the regulation of LuxS of Strecptococcus mutans., Methods: The differences in biofilm formation and aciduricity of Strecptococcus mutans among the methyl-metabolism-complementation strain (KO-S), the parental wide-type strain (WT) and the luxS null strain (KO) were observed by real-time PCR for monitoring the transcriptional level of genes related to biofilm formation (smu.238, gtfD) and aciduricity (smu.44, smu.46) of the studied strains, methyl thiazolyl tetrazolium (MTT) for quantifying the biofilm of the exhibited strains and confocal laser scanning microscopy for estimating the structure of the biofilm., Results: The transcriptional level of smu.44, smu.46, smu.238, gtfD in WT were 1.289 ± 0.051, 1.694 ± 0.140, 1.565 ± 0.107, 1.667 ± 0.196 respectively; in KO were 1.001 ± 0.045, 1.007 ± 0.151, 1.000 ± 0.021, 1.012 ± 0.196 respectively, downregulated compared with WT (P < 0.05); in KO-S were 4.662 ± 0.091, 5.019 ± 0.258, 3.462±0.029, 3.071 ± 0.136 respectively, upregulated compared both with KO and with WT (P < 0.05). The quantity of biofilms formed by the studied strains were WT (1.592 ± 0.213), KO (0.939 ± 0.029), KO- S (2.177 ± 0.226), KO- P (1.020 ± 0.093), respectively, representing a less quantity by KO and KO-P than WT (P < 0.05) and a more quantity by KO-S than other three stains (P < 0.05). According to the observation of biofilms texture by confocal laser scanning microscopy, the WT biofilm was condensed and even. In contrast, fissures and gaps were found scattered in biofilms of KO, KO-P while lessened in that of KO-S, in which high-density bacterial aggregates were observed. The acid assay indicated a smaller biofilm decrease by WT and KO-S than that by KO and KO- P(P < 0.05)., Conclusions: The methyl- metabolism pathway contributes to LuxS regulation on biofilm formation and auiduricity of Strecptococcus mutans.

Recent technological advances have made it possible to carry out high-throughput metabonomics studies using gas chromatography coupled with time-of-flight mass spectrometry. Large volumes of data are produced from these studies and there is a pressing need for algorithms that can efficiently process and analyze data in a high-throughput fashion as well. We present an Automated Data Analysis Pipeline (ADAP) that has been developed for this purpose. ADAP consists of peak detection, deconvolution, peak alignment, and library search. It allows data to flow seamlessly through the analysis steps without any human intervention and features two novel algorithms in the analysis. Specifically, clustering is successfully applied in deconvolution to resolve coeluting compounds that are very common in complex samples and a two-phase alignment process has been implemented to enhance alignment accuracy. ADAP is written in standard C++ and R and uses parallel computing via Message Passing Interface for fast peak detection and deconvolution. ADAP has been applied to analyze both mixed standards samples and serum samples and identified and quantified metabolites successfully. ADAP is available at http://www.du-lab.org .

DNA methylation is an important epigenetic phenomenon that is associated with a variety of diseases, particularly cancers. Recent development of high throughput sequencing technology has enabled researchers to investigate the methylation rate at a single nucleotide resolution for any given sample. Testing for methylation rate equality or difference between two samples, however, is challenged by the small sample size observed at many sites across the genome. Fisher's exact test is typically used in this situation; however, it is conservative and it cannot be used to test for specific difference in methylation rate between two samples. In this paper, we propose an empirical Bayes approach that utilizes the genome-wide data as prior information for methylation differentiation between two samples. We show that this new approach is more powerful than Fisher's exact test. In addition, it can be used to test for any specific methylation difference while controlling the false discovery rate (FDR). The new method is applied to a real data set from a colon tumor study.