Matrixed CDR grafting: A neoclassical framework for antibody humanization and developability.

Discovery and optimization of a biotherapeutic monoclonal antibody requires a careful balance of target engagement and physicochemical developability properties. To take full advantage of the sequence diversity provided by different antibody discovery platforms, a rapid and reliable process for humanization of antibodies from nonhuman sources is required. Canonically, maximizing homology of the human variable region (V-region) to the original germline was believed to result in preservation of binding, often without much consideration for inherent molecular properties. We expand on this approach by grafting the complementary determining regions (CDRs) of a mouse anti-LAG3 antibody into an extensive matrix of human variable heavy chain (VH) and variable light chain (VL) framework regions with substantially broader sequence homology to assess the impact on complementary determining region-framework compatibility through progressive evaluation of expression, affinity, biophysical developability, and function. Specific VH and VL framework sequences were associated with major expression and purification phenotypes. Greater VL sequence conservation was correlated with retained or improved affinity. Analysis of grafts that bound the target demonstrated that initial developability criteria were significantly impacted by VH, but not VL. In contrast, cell binding and functional characteristics were significantly impacted by VL, but not VH. Principal component analysis of all factors identified multiple grafts that exhibited more favorable antibody properties, notably with nonoptimal sequence conservation. Overall, this study demonstrates that modern throughput systems enable a more thorough, customizable, and systematic analysis of graft-framework combinations, resulting in humanized antibodies with improved global properties that may progress through development more quickly and with a greater probability of success.

Evolution of fermented grain yeast communities in strong-flavored baijiu and functional validation of yeasts that produce superior-flavored substances.

BACKGROUND: Baijiu is a well-known alcoholic beverage in China and the quality is determined by various microorganisms during the fermentation process. Yeast is one of the most important microorganisms in the fermentation of baijiu. It has a strong esterification capacity and also affects the aroma. RESULTS: High-throughput sequencing results showed that the fermented grains (jiupei) during baijiu production were mainly composed of eight highly abundant yeast species. The species and abundance of yeasts changed significantly with the fermentation process. The flavor of 30 yeast strains in the jiupei was determined by a sniffing test and gas chromatography-mass spectrometry (GC-MS). The strain with the highest flavor substance content (2.34 mg L-1), named YX3205, was identified as Clavispora lusitaniae. Tolerance results showed that C. lusitaniae YX3205 can tolerate up to 15% (v v-1) ethanol. In a solid-state simulated fermentation experiment, the content of 24 flavor substances was significantly increased in the fortified group, and the total ester content reached 4240.73 µg kg-1, which was 2.8 times higher than that of the control group. CONCLUSION: The present study demonstrated the potential of C. lusitaniae YX3205 to enhance the flavor of baijiu, thereby serving as a valuable strain for the improvement of the flavor quality of baijiu. © 2024 Society of Chemical Industry.

Multiparametric magnetic resonance imaging-derived radiomics for the prediction of disease-free survival in early-stage squamous cervical cancer.

OBJECTIVE: To conduct multiparametric magnetic resonance imaging (MRI)-derived radiomics based on multi-scale tumor region for predicting disease-free survival (DFS) in early-stage squamous cervical cancer (ESSCC). METHODS: A total of 191 ESSCC patients (training cohort, n = 135; validation cohort, n = 56) from March 2016 to September 2019 were retrospectively recruited. Radiomics features were derived from the T2-weighted imaging (T2WI), contrast-enhanced T1-weighted imaging (CET1WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) map for each patient. DFS-related radiomics features were selected in 3 target tumor volumes (VOIentire, VOI+5 mm, and VOI-5 mm) to build 3 rad-scores using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Logistic regression was applied to build combined model incorporating rad-scores with clinical risk factors and compared with clinical model alone. Kaplan-Meier analysis was used to further validate prognostic value of selected clinical and radiomics characteristics. RESULTS: Three radiomics scores all showed favorable performances in DFS prediction. Rad-score (VOI+5 mm) performed best with a C-index of 0.750 in the training set and 0.839 in the validation set. Combined model was constructed by incorporating age categorized by 55, Federation of Gynecology and Obstetrics (Figo) stage, and lymphovascular space invasion with rad-score (VOI+5 mm). Combined model performed better than clinical model in DFS prediction in both the training set (C-index 0.815 vs 0.709; p = 0.024) and the validation set (C-index 0.866 vs 0.719; p = 0.001). CONCLUSION: Multiparametric MRI-derived radiomics based on multi-scale tumor region can aid in the prediction of DFS for ESSCC patients, thereby facilitating clinical decision-making. KEY POINTS: • Three radiomics scores based on multi-scale tumor region all showed favorable performances in DFS prediction. Rad-score (VOI+5 mm) performed best with favorable C-index values. • Combined model incorporating multiparametric MRI-based radiomics with clinical risk factors performed significantly better in DFS prediction than the clinical model. • Combined model presented as a nomogram can be easily used to predict survival, thereby facilitating clinical decision-making.

ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome.

BACKGROUND: It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development. METHODS: We measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis. RESULTS: Compared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS. CONCLUSIONS: ANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS.

New insights into the effects of caffeine on adult hippocampal neurogenesis in stressed mice: Inhibition of CORT-induced microglia activation.

Chronic stress-evoked depression has been implied to associate with the decline of adult hippocampal neurogenesis. Caffeine has been known to combat stress-evoked depression. Herein, we aim to investigate whether the protective effect of caffeine on depression is related with improving adult hippocampus neurogenesis and explore the mechanisms. Mouse chronic water immersion restraint stress (CWIRS) model, corticosterone (CORT)-established cell stress model, a coculture system containing CORT-treated BV-2 cells and hippocampal neural stem cells (NSCs) were utilized. Results showed that CWIRS caused obvious depressive-like disorders, abnormal 5-HT signaling, and elevated-plasma CORT levels. Notably, microglia activation-evoked brain inflammation and inhibited neurogenesis were also observed in the hippocampus of stressed mice. In comparison, intragastric administration of caffeine (10 and 20 mg/kg, 28 days) significantly reverted CWIRS-induced depressive behaviors, neurogenesis recession and microglia activation in the hippocampus. Further evidences from both in vivo and in vitro mechanistic experiments demonstrated that caffeine treatment significantly suppressed microglia activation via the A2AR/MEK/ERK/NF-κB signaling pathway. The results suggested that CORT-induced microglia activation contributes to stress-mediated neurogenesis recession. The antidepression effect of caffeine was associated with unlocking microglia activation-induced neurogenesis inhibition.

Antifungal susceptibility testing with YeastONE™ is not predictive of clinical outcomes of Cryptococcus neoformans var. grubii fungemia.

Mortality rates due to Cryptococcus neoformans var. grubii fungemia remain significant despite treatment with antifungal drugs. The predictive function of antifungal susceptibility and its correlation with treatment outcome remains controversial. A retrospective study was conducted from January 1, 2009, to December 31, 2016, on 85 patients with C. neoformans var. grubii fungemia confirmed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Antifungal drug susceptibility was determined using the YeastONE™ colorimetric broth microdilution method coupled with Vizion™ System following the Clinical and Laboratory Standards Institute guidelines. Six antifungal agents-amphotericin B, fluconazole, flucytosine, itraconazole, posaconazole, and voriconazole-were tested. The patients' demographic data and clinical information were abstracted for further analyses. Antifungal regimens consisting of amphotericin B with or without fluconazole or flucytosine were administered for induction treatment of these patients, followed with intravenous or oral fluconazole for maintenance therapy. Clinical outcomes were defined by 14- and 30-day mortality rates. Risk factors associated with outcomes were fitted in a logistic regression model by univariate or multivariate method. Eighty-five patients with C. neoformans var. grubii fungemia were enrolled in the study. The Sequential Organ Failure Assessment Score, Glasgow Coma Scale, Charlson comorbidity score, and adequate duration of therapy for amphotericin B were predictors for mortality in univariate analysis. Antifungal susceptibility testing with YeastONE™ does not predict clinical outcomes of C. neoformans var. grubii fungemia. Greater disease severity, high comorbidities, poor consciousness level, and inappropriate treatment were associated with increased mortality in cryptococcemia cases.

Cryptococcus neoformans is an encapsulated yeast living in both plants and animals that is composed of three main serotypes: C. neoformans var. grubii, C. neoformans var. gattii, and C. neoformans var. neoformans. C. neoformans var. grubii is the most common disease-causing Cryptococcus species worldwide. C. neoformans var. gattii is more prevalent than C. neoformans var. neoformans in both tropical and subtropical regions of Asia. C. neoformans causes severe, even fatal, diseases such as pulmonary infection, bloodstream infection, skin and soft tissue infection, bone and joint infection, central nervous system infection, and disseminated infection, regardless of host immunocompetence. We conducted a retrospective study on 85 patients who contracted cryptococcemia from January 1, 2009, to December 31, 2016. This work conducted both microbiological and clinical studies involving in vitro susceptibility testing, demographic data, comorbidities, treatment modalities, and treatment outcomes. We utilized a modern medical technique-based instrument, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS; Biotyper, Bruker Daltonics, Inc.), which determines the unique proteomic fingerprint of an organism, to identify the C. neoformans serotype. We utilized Thermo Fisher Scientific™ Sensititre™ YeastONE™ colorimetric broth microdilution plates coupled with a Vizion™ Digital MIC Viewing System (a computer-assisted optical reading machine) to determine the in vitro susceptibility of amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, and voriconazole against 85 C. neoformans var. grubii blood isolates. In conclusion, the susceptibility patterns of these antifungal agents did not correlate significantly with treatment outcomes. However, a lower disease severity score, a lower Glasgow Coma Scale score, fewer comorbidities, and adequate amphotericin B treatment duration were predictors for treatment success in univariate analysis.

Serum and urine ANGPTL8 expression levels are associated with hyperlipidemia and proteinuria in primary nephrotic syndrome.

BACKGROUND: This study aimed to investigate the expression characteristics of ANGPTL8 in patients with primary nephrotic syndrome and its possible correlation with hyperlipidemia and proteinuria. METHODS: ANGPTL8 levels were determined using an enzyme-linked immunosorbent assay in 133 subjects with PNS and 60 healthy controls. RESULTS: Compared with healthy controls, subjects with primary nephrotic syndrome had higher levels of serum and urine ANGPTL8 (P < 0.001). In primary nephrotic syndrome patients, serum ANGPTL8 was positively correlated with cholesterol (r = 0.209, P < 0.05) and triglycerides (r = 0.412, P < 0.001), while there was no correlation with 24 hUTP. Urine ANGPTL8 was positively correlated with high-density lipoprotein cholesterol (r = 0.181, P < 0.05) and was significantly negatively correlated with creatinine (r = - 0.323, P < 0.001), eGFR (r = - 0, P < 0.001) and 24 hUTP (r = - 0.268, P = 0.002). Interestingly, the urine ANGPTL8 concentrations in membranous nephropathy and mesangial proliferative glomerulonephritis pathological types were different. CONCLUSIONS: Serum and urine ANGPTL8 levels in primary nephrotic syndrome patients were correlated with blood lipid levels and proteinuria, respectively, suggesting that ANGPTL8 may play a role in the development of primary nephrotic syndrome hyperlipidemia and proteinuria.

Neutrophilic granule protein (NGP) attenuates lipopolysaccharide-induced inflammatory responses and enhances phagocytosis of bacteria by macrophages.

Neutrophilic granule protein (NGP) belongs to the cystatin superfamily. Even though this superfamily is critically involved in cancer biology and adaptive immunity, the relationship of macrophage NGP to inflammation and phagocytosis remains poorly understood. In this study, we observed a significant increase of NGP in peritoneal macrophages (PMs) isolated from mice challenged with E. coli or lipopolysaccharide (LPS), as judged by NGP mRNA microarray. We also found changes in NGP to be mainly Toll-like receptor 4 (TLR4)-dependent. By western blot and electrophoretic mobility shift assay, we demonstrated NGP overexpression to reduce TNF-α and IL-1ß production by LPS-induced RAW264.7 cells (RAW) via suppression of the NF-κB (p65 and p50) signalling pathway, rather than the JNK1/AP-1 (fos and jun) signalling pathway. NGP overexpression by LPS-induced RAW also induced IL-10, an anti-inflammatory cytokine, which was partially involved in the anti-inflammatory effect produced by NGP overexpression. Moreover, upregulated NGP enhanced the phagocytosis of E. coli by RAW. Taken together, these results demonstrated NGP to be an important host defense component that regulates inflammatory responses and phagocytosis by activated macrophages. As such, NGP may be useful for the treatment of inflammatory based disease.

[Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases].

OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS: COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.

MicroRNA-329-mediated PTTG1 downregulation inactivates the MAPK signaling pathway to suppress cell proliferation and tumor growth in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a severe malignancy usually producing a poor prognosis and high mortality rate. MicroRNAs (miRNAs) have been reported in association with CCA; however, the role miR-329 plays in the CCA condition still remains unclear. Therefore, this study was conducted to explore the underlying mechanism of which miR-329 is influencing the progression of CCA. This work studied the differential analysis of the expression chips of CCA obtained from the Gene Expression Omnibus database. Next, to determine both the expression and role of pituitary tumor transforming gene-1 (PTTG1) in CCA, the miRNAs regulating PTTG1 were predicted. In the CCA cells that had been intervened with miR-329 upregulation or inhibition, along with PTTG1 silencing, expression of miR-329, PTTG1, p-p38/p38, p-ERK5/ERK5, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bcl-2-associated X protein (Bax), B-cell CLL/lymphoma 2 (Bcl-2), and caspase-3 were determined. The effects of both miR-329 and PTTG1 on cell proliferation, cell-cycle distribution, and apoptosis were also assayed. The miR-329 was likely to affect the CCA development through regulation of the PTTG1-mediated mitogen-activated protein kinase (MAPK) signaling pathway. The miR-329 targeted PTTG1, leading to inactivation of the MAPK signaling pathway. Upregulation of miR-329 and silencing of PTTG1 inhibited the CCA cell proliferation, induced cell-cycle arrest, and subsequently promoted apoptosis with elevations in Bax, cleaved caspase-3, and total caspase-3, but showed declines in PCNA, Cyclin D1, and Bcl-2. Moreover, miR-329 was also found to suppress the tumor growth by downregulation of PTTG1. To summarize, miR-329 inhibited the expression of PTTG1 to inactivate the MAPK signaling pathway, thus suppressing the CCA progression, thereby providing a therapeutic basis for the CCA treatment.

Effects of small interfering RNA targeting TLR4 on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome with hypertension in a rat model.

We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real-time polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference-mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.

Soluble Egg Antigen Activates M2 Macrophages via the STAT6 and PI3K Pathways, and Schistosoma Japonicum Alternatively Activates Macrophage Polarization to Improve the Survival Rate of Septic Mice.

Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti-inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS-induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-ß1 expression; inhibited TNF-α and iNOS expression; and blocked the effect of LPS-promoted TNF-α and iNOS expression. Furthermore, adoptive transfer of ex vivo programed M2 macrophages significantly increased the survival rate of septic mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played the same role as worm infection but had no impact on M1 macrophages. SEA reduced LPS-induced TNF-α and iNOS expression, decreased the inhibitory effect of LPS on IL-10 and TGF-ß1 expression, increased STAT6 phosphorylation, and up-regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be reduced. Therefore, worm infection has a protective effect in septic mice in which SEA may play a key role via the STAT6 and PI3K pathways. This finding may provide a favorable solution for the treatment of sepsis, especially early cases. J. Cell. Biochem. 118: 4230-4239, 2017. © 2017 Wiley Periodicals, Inc.

Construction of Covalent Organic Frameworks Bearing Three Different Kinds of Pores through the Heterostructural Mixed Linker Strategy.

It is very important to create novel topologies and improve structural complexity for covalent organic frameworks (COFs) that might lead to unprecedented properties and applications. Despite the progress achieved over the past decade, the structural diversity and complexity of COFs are quite limited. In this Communication, we report the construction of COFs bearing three different kinds of pores through the heterostructural mixed linker strategy involving the condensation of a D2h-symmetric tetraamine and two C2-symmetric dialdehydes of different lengths. The complicated structures of the triple-pore COFs have been confirmed by powder X-ray diffraction and pore size distribution analyses.

[Study of the Detection of Histidine Based on "On-Off" Fluorescence Probe of Carbon Dots].

An new type of switch "On-Off" fluorescence probe was constructed based on fluorescence carbon dots as a novel strategy to analyze trace histidine(His) which was proposed for the first time. In water solution with pH 7.6, the fluorescence of CDs was quenched with Ru3+ due to the formation of ground state compound through electrostatic attraction, and the system was thus "turned-off". The fluorescence intensity of CDs was "turned-on" due to the competition between His and Ru towards the surface of CDs. The effect of critical parameters including pH, buffer solutions, reaction temperature and time needed to grow the fluorescence intensity of CDs was studied. Results show thatin water solution with pH 7.6, and when the temperature was between 20~25 ℃, the fluorescence intensity of the released CDs displayed a linear relationship in the range of (6.5~219.3)×10-6 mol·L-1 of captopril. Lower limit of detection for His, at the signal-to-noise ratio of 3/(3δ), was 2.15×10-6 mol·L-1. The methodology was successfully applied for the determination of His in Compound Amino Acid Injections, with the RSD≤2.07%, and the recovery rate was between 95.7%～102.4%. The result of the experiment was satisfactory. On the one hand, the excellent optical character CDs was acted as "On-Off" fluorescence probe, which could be extent the application of CDs, on the other hand, the excellent performance of the proposed fluorescence probe shows that this method possesses the potential for practical application.

Micrometam C Protects against Oxidative Stress in Inflammation Models in Zebrafish and RAW264.7 Macrophages.

Micrometam C is a core of novel marine compound isolated from the mangrove associates Micromelum falcatum. In this study, we investigated the protective effects of micrometam C in inflammation models in the transgenic zebrafish line Tg (corola: eGFP) and RAW264.7 macrophages. We found that micrometam C significantly suppressed the migration of immune cells in tail-cutting-induced inflammation in transgenic zebrafish and reduced lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) in both zebrafish and macrophages. In addition, micrometam C also restored LPS-induced reduction of endogenous antioxidants, such as catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). The protective effects of micrometam C were in parallel to its inhibition of NADPH oxidase and nuclear factor-kappa-binding (NF-κB) activity. Thus, the present results demonstrate that micrometam C protects against LPS-induced inflammation possibly through its antioxidant property.

A natural product, resveratrol, protects against high-glucose-induced developmental damage in chicken embryo.

Resveratrol, a famous plant-derived polyphenolic phytoalexin, has been considered to play physiological roles such as antioxidative, neuroprotective, and anticancer effects in adults. However, its antioxidative activity and neuroprotective effect were seldom discussed in the embryonic system. In this study, the effect of resveratrol on chicken embryo development under high glucose and its underlying mechanism of resveratrol were investigated. High glucose administrated to chicken embryo at embryonic Day 1 induced stillbirth, growth retardation, and impaired blood vessel development on yolk sac. However, resveratrol supplementation before glucose exposure showed significant effect on decreasing the death rate, developmental damage, and vessel injury. In addition, oxidative stress was caused by high-glucose exposure, and resveratrol could rescue this high-glucose-induced oxidative stress. Moreover, the neural developmental marker paired box 3 was significantly decreased by high glucose and recovered by resveratrol. Cell cycle-regulated gene expression was also intervened by resveratrol. This study had found an association between resveratrol and hyperglycemia-induced embryonic damage, which suggested a potential protective effect of resveratrol on gestational diabetes.

Differing chemical compositions of three teas may explain their different effects on acute blood pressure in spontaneously hypertensive rats.

BACKGROUND: Heavy tea consumption is suggested to be unsuitable for hypertensive people. However, the bioactive substances in different varieties of tea leaves are very different. This study compares the effects of three Chinese teas - C. sinensis, C. ptilophylla and C. assamica var. kucha - on blood pressure (BP) and heart rate in spontaneously hypertensive rats (SHRs). RESULTS: Intragastric administration of C. sinensis extract led to an acute increase in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate in SHRs. However, C. ptilophylla and C. assamica var. kucha exerted no obvious influences on SBP, DBP or heart rate. Similar to the extract of C. sinensis, intragastric administration of caffeine also led to an acute increase in BP and heart rate in SHRs. In contrast, theobromine and theacrine - purine alkaloids predominantly contained in C. ptilophylla and C. assamica var. kucha, respectively - had no pressor effects. The effect of caffeine on BP was related to the regulation of plasma epinephrine and norepinephrine levels in SHRs. CONCLUSION: The different effects of C. sinensis, C. ptilophylla and C. assamica var. kucha on BP might be explained, at least partially, by the differences in the varieties and contents of purine alkaloids.

One-step construction of two different kinds of pores in a 2D covalent organic framework.

Covalent organic frameworks (COFs) are crystalline porous materials bearing microporous or mesoporous pores. The type and size of pores play crucial roles in regulating the properties of COFs. In this work, a novel COF, which bears two different kinds of ordered pores with controllable sizes: one within microporous range (7.1 Å) and the other in mesoporous range (26.9 Å), has been constructed via one-step synthesis. The structure of the dual-pore COF was confirmed by PXRD investigation, nitrogen adsorption-desorption study, and theoretical calculations.

Effects of oral probiotics on inflammation and intestinal function in adult patients after appendectomy: Randomized controlled trial.

BACKGROUND: Appendectomy is an acute abdominal surgery that is often accompanied by severe abdominal inflammation. Oral probiotics are one of the postoperative treatments for rapid rehabilitation. However, there is a lack of prospective studies on this topic after appendectomy. AIM: To investigate whether the postoperative probiotics can modulate the inflammatory response and restore intestinal function in patients following appendectomy. METHODS: This was a prospective, randomized trial. A total of 60 emergency patients were randomly divided into a control group (n = 30) and a probiotic group (n = 30). Patients in the control group started to drink some water the first day after surgery, and those in the probiotic group were given water supplemented with Bacillus licheniformis capsules for 5 consecutive days postsurgery. The indices of inflammation and postoperative conditions were recorded, and the data were analyzed with RStudio 4.3.2 software. RESULTS: A total of 60 participants were included. Compared with those in the control group, the C-reactive protein (CRP), interleukin 6 and procalcitonin (PCT) levels were significantly lower in the probiotic group at 2 d after surgery (P = 2.224e-05, P = 0.037, and P = 0.002, respectively, all P < 0.05). This trend persisted at day 5 post-surgery, with CRP and PCT levels remaining significantly lower in the probiotic group (P = 0.001 and P = 0.043, both P < 0.05). Furthermore, probiotics resulted in a shorter time to first flatus and a greater percentage of gram-negative bacilli in the feces (P = 0.035, P = 0.028, both P < 0.05). CONCLUSION: Postoperative oral administration of probiotics may modulate the gut microbiota, benefit the recovery of the early inflammatory response, and subsequently enhance recovery after appendectomy.

Salidroside protects RGC from pyroptosis in diabetes-induced retinopathy associated with NLRP3, NFEZL2 and NGKB1, revealed by network pharmacology analysis and experimental validation.

OBJECTIVE: To investigate the effect of salidroside (SAL) in protecting retinal ganglion cell (RGC) from pyroptosis and explore associated molecular network mechanism in diabetic retinapathy (DR) rats. METHODS: HE, Nissl and immunofluorescence staining were used to observe the retinal morphological change, and the related target genes for salidroside, DR and pyroptosis were downloaded from GeneCard database. Then Venny, PPI, GO, KEGG analysis and molecular docking were used to reveal molecular network mechanism of SAL in inhibiting the pyroptosis of RGC. Lastly, all hub genes were confirmed by using qPCR. RESULTS: HE and Nissl staining showed that SAL could improve the pathological structure known as pyroptosis in diabetic retina, and the fluorescence detection of pyroptosis marker in DM group was the strongest, while they decreased in the SAL group(P < 0.05)). Network pharmacological analysis showed 6 intersecting genes were obtained by venny analysis. GO and KEGG analysis showed 9 biological process, 3 molecular function and 3 signaling pathways were involved. Importantly, molecular docking showed that NFE2L2, NFKB1, NLRP3, PARK2 and SIRT1 could combine with salidroside, and qPCR validates the convincible change of CASP3, NFE2L2, NFKB1, NLRP3, PARK2 and SIRT1. CONCLUSION: Salidroside can significantly improve diabetes-inducedRGC pyrotosis in retina, in which, the underlying mechanism is associated with the NLRP3, NFEZL2 and NGKB1 regulation.