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In this study, a copper hexacyanoferrate nanoparticle with excellent oxidase-mimetic behaviour has been synthesized through a simple precipitation method. The synthesized copper hexacyanoferrate nanoparticle has intrinsic oxidase-like activity, which can catalyze the chromogenic reaction of 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) through an O2•− reactive oxygen-species-participated process. On the other hand, K3[Fe(CN)6] can be reduced by ascorbic acid (AA) to produce K4[Fe(CN)6], thereby inhibiting the formation of the copper hexacyanoferrate nanoparticles. Furthermore, ascorbate oxidase (AAO) can catalyze the oxidation of AA to produce dehydroascorbic acid, which cannot reduce K3[Fe(CN)6]. Thus, a system for an AAO-regulated in situ formation of copper hexacyanoferrate nanoparticles was constructed by coupling a prepared copper hexacyanoferrate nanozyme with AA for the detection of AAO activity. This colorimetric sensing assay shows high sensitivity and selectivity for the detection of AAO activity (the limit of detection is 0.52 U/L) with a linear range of 1.1–35.7 U/L. Finally, the developed method was applied to detect the activity of AAO in normal human serum with a satisfactory sample spiked recovery (87.4–108.8%). In short, this study provides a good strategy for the construction of nanozyme-based multi-enzyme cascade-signal amplification assay.

(1) Background: Single blastocyst transfers (SBT) and double blastocyst transfers (DBT) are widely used in clinical practice. The objective of this study was to investigate the application of these two strategies in women of different ages. (2) Methods: Analysis was carried out on 5477 frozen embryo transfer cycles of women in different ages. All the cycles were divided into three groups according to the age of the included women: 39. The live birth rate (LBR) and multiple birth rate (MBR) between the SBT and DBT among these groups, respectively, were compared. (3) Results: In the women < 35 group, the LBR was similar in SBT and DBT, but the MBR was higher in DBT than SBT. In women 35–39, with >10 oocytes retrieved, the MBR in DBT was significantly higher than SBT, but there was no significant difference in LBR between the two groups; with ≤10 oocytes retrieved, the LBR in DBT were significantly higher than SBT, but the MBT was not significantly different between the two groups. In women > 39, the LBR and MBR were lower in the SBT than DBT, but the differences were not statistically significant. (4) Conclusions: Selective SET is appropriate for most young women, whereas older women are advised to make individualized choices based on the number of oocytes retrieved and blastocyst quality.

Anthocyanins are important pigments that contribute to fruit quality. The regulation of anthocyanin biosynthesis by several transcription factors via sophisticated regulatory networks has been studied in various plants. Brassinosteroids (BRs), a new class of plant hormone, are involved in regulating anthocyanin biosynthesis in fruits. Furthermore, light directly affects the synthesis and distribution of anthocyanins. Here, we summarize the recent progress toward understanding the impact of BR and light on anthocyanin biosynthesis in climacteric and non-climacteric fruits. We review the BR and light signaling pathways and highlight the important transcription factors that are associated with the synthesis of anthocyanins, such as BZR1 (brassinazole-resistant 1, BR signaling pathway), HY5 (elongated hypocotyl 5) and COP1 (constitutively photomorphogenic 1, light signal transduction pathway), which bind with the target genes involved in anthocyanin synthesis. In addition, we review the mechanism by which light signals interact with hormonal signals to regulate anthocyanin biosynthesis.

Background Septic shock is associated with increased mortality. Predicting mortality, including early prediction for septic shock patients in intensive care units (ICUs), remains an important challenge. Method We searched the Medical Information Mart for Intensive Care IV database. Odds ratios (ORs) with 95% confidence intervals (CIs) of the relationships between shock index (SI), modified SI (MSI), and diastolic SI (DSI) of patients with septic shock requiring vasopressors and 3-day/in-hospital mortality were calculated using logistic regression models. The time-course changes of these parameters were compared between survivors and non-survivors. The performance of the different parameters was described by the area under the receiver operating characteristic (ROC) curve (AUC) and compared with DeLong analysis. Results A total of 1266 patients with septic shock requiring vasopressors were identified. The 3-day mortality rate and in-hospital mortality rate were 8.7% and 23.5%, respectively. Multivariable logistic regression analysis showed significant associations between pre-vasopressor SI/MSI/DSI and 3-day mortality in patients with septic shock requiring vasopressors in fully adjusted models (Ps for trend P Conclusion Pre-vasopressor SI, MSI, and DSI values identified patients with septic shock requiring vasopressors who are at increased risk of early death. Of these easy-to-acquire values, SI and MSI show a comparatively better performance.

Surface-enhanced Raman scattering is a rapid, highly sensitive and non-destructive technique, whereas, it was still limited to designing different types of enhancing substrates or using probe molecules to only identify single biomolecules. Especially, some special biomolecules have weak Raman signals in solid state, so it is a huge challenge to obtain their enhanced Raman signals in liquid. To solve the problem, a double-enhanced Raman scattering (DERS) detection platform was developed in this study based on silver nanoparticles that were prepared by using an appropriate amount of sodium borohydride and guided by calcium ions to form good "hot spots". This enabled one to successfully obtain fingerprints of various types of biomolecules under the identical experimental conditions. The addition of sodium borohydride as reducing agent could protect silver nanoparticles from oxidation, and biomolecules were adsorbed on the exposed silver surface and demonstrated their initially enhanced Raman signals. Furthermore, the "hot spots" formed by silver nanoparticles without silver oxide coating could further enhance the Raman signal of biomolecules, making the enhancement factor up to 10 [8]. To sum up, the possibility of fast identification of different species of biomolecules via DERS has wide application prospects in the fields of biomarker detection and medical diagnosis.

While sarcopenia is an important clinical finding in individuals diagnosed with chronic heart failure (CHF), efforts to identify a reliable biomarker capable of predicting the overall muscular and functional decline in CHF patients have been unsuccessful to date.The objectives of this study were to study the diagnostic utility of MicroRNA (miRNA)-1-3p as a predictor of sarcopenia status in individuals diagnosed with CHF.In total, 80 individuals with heart failure exhibiting a left ventricular ejection fraction50% were enrolled in this study. All patients were analyzed to assess miR-1-3p expression levels, with body composition being evaluated through dual-energy X-ray absorptiometry and sarcopenia being defined based on the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength (HGS). In addition, the activation of the Akt/mTOR signaling pathway was evaluated in these individuals.In total, 40 of the enrolled patients (50%) exhibited sarcopenia. Sarcopenic patients presented with increased miR-1-3p expression levels as compared to non-sarcopenic individuals (1.69 ± 0.132 vs. 1.22 ± 0.106; p0.05). With respect to sarcopenic indices, appendicular skeletal mass index was most strongly correlated with miR-1-3p expression, which was also strongly correlated with HGS. High levels of Akt/mTOR signaling pathway components were expressed in sarcopenic individuals, highlighting a significant relationship between miR-1-3p activity and signaling through this pathway. Moreover, miR-1-3p was identified as a specific marker for sarcopenia in individuals with CHF.These results suggest that circulating miR-1-3p levels are related to Akt/mTOR pathway activation and can offer valuable insight into the overall physical capacity and muscular integrity of CHF patients as a predictor of sarcopenia. (Rev Invest Clin. 2022;74(5):276-83).

Covalent adaptable liquid crystal networks (CALCNs) are highly potential actuating materials due to their actuation properties and shape reprogrammability. Given the importance of network crosslinking state in a CALCN actuator, we sought an all-in-one strategy to probe and visualize its dynamic network while ensuring actuation and reprogramming. Here, tetraphenylethylene derivatives were incorporated into liquid crystal networks via the Diels-Alder (DA) reaction, acting simultaneously as reversible crosslinkers and aggregation-induced emission (AIE) fluorescent probes. The thermally tunable fluorescence of the resulting network can correlate to and thus visualize the actuator's crosslinking status, actuation capability and temperature in real-time and in situ, yielding an intriguing actuation limit-alerting function. Furthermore, we verified unprecedented reprogrammability of the AIE-type CALCNs through both associative and dissociative exchange mechanisms of DA chemistry.

Tea plant, an important beverage crop, is cultivated worldwide. Lignification can improve the hardness of tea plant, which is of great significance for tea quality. Jasmonates (JAs) and cytokinin are plant hormones that control processes of plant development and secondary metabolite accumulation. Hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT) is primarily involved in lignin biosynthesis. The effects of exogenous application of JAs and cytokinin on lignin biosynthesis and related HCT gene expression profiles in tea plants are still unclear. In order to investigate the effects of exogenous JAs and cytokinin on lignin accumulation, anatomical structures, and CsHCT gene profiles in tea plants, we treated tea plants with methyl jasmonate (MeJA) and cytokinin (6-BA). MeJA and 6-BA treatments triggered the lignification at 6 and 12 d in tea leaves. The combined treatment resulted in an increase in lignin content at 6 d, which was 1.32 times of that at 0 d for 'Mengshan 9.' The CsHCTs in clade 2 (CsHCT5, CsHCT6, CsHCT7, and CsHCT8) were mainly expressed in leaves. We found that exogenous MeJA and cytokinin might be able to antagonistically regulate tea plant lignin accumulation through the mediation of CsHCT expression. This study revealed that HCTs play potential important roles involved in lignin biosynthesis of tea plant development and hormonal stimuli.

Nitrate nitrogen is an important nitrogen source for tea plants’ growth and development. LBD transcription factors play important roles in response to the presence of nitrate in plants. The functional study of LBD transcription factors in tea plants remains limited. In this study, the LBD family gene CsLBD39 was isolated and characterized from tea plants. Sequence analysis indicated that CsLBD39 contained a highly conserved CX2CX6CX3CX domain. The phylogenetic tree assay showed that CsLBD39 belonged to class II subfamily of the LBD family. CsLBD39 was highly expressed in flowers and root; we determined that its expression could be induced by nitrate treatment. The CsLBD39 protein was located in the nucleus and has transcriptional activation activity in yeast. Compared with the wild type, overexpression of CsLBD39 gene in Arabidopsis resulted in smaller rosettes, shorter main roots, reduced lateral roots and lower plant weights. The nitrate content and the expression levels of genes related to nitrate transport and regulation were decreased in transgenic Arabidopsis hosting CsLBD39 gene. Compared with the wild type, CsLBD39 overexpression in transgenic Arabidopsis had smaller cell structure of leaves, shorter diameter of stem cross section, and slender and compact cell of stem longitudinal section. Under KNO3 treatment, the contents of nitrate, anthocyanins, and chlorophyll in leaves, and the content of nitrate in roots of Arabidopsis overexpressing CsLBD39 were reduced, the expression levels of nitrate transport and regulation related genes were decreased. The results revealed that CsLBD39 may be involved in nitrate signal transduction in tea plants as a negative regulator and laid the groundwork for future studies into the mechanism of nitrate response.

Adult brainstem gliomas are rare central nervous system tumors that represent a heterogeneous group of tumors. Somatic IDH mutations are uncommon in adult brainstem gliomas and there are few relevant clinical studies. Here, we reported five patients with IDH1 mutations associated with brainstem gliomas, including four cases of IDH1 R132H mutations and one case of R132G mutation. All patients were treated with focal intensity-modulated radiation therapy (IMRT) with concurrent temozolomide (TMZ). One patient died, one relapsed, and three survived to date. All these cases carried a pathogenic variant of TP53, among whom 1 harbored ATRX mutation and 1 had H3K27M mutation. Moreover, we also found some genes related to a worse prognosis, such as CDK4/6 amplification. These findings demonstrate that the specific characteristics of IDH-mutant brainstem gliomas should be considered in diagnostic workflows to make therapeutic regimens and improve the prognosis.

The impact of etiologies of acute fulminant myocarditis (AFM), which requires extracorporeal membrane oxygenation (ECMO), on clinical outcomes remains unknown. This study aimed to investigate the risk factors for ECMO weaning and mortality among patients with AFM due to viral etiologies in a tertiary referral medical center.We included 33 adults with AFM who received ECMO and were admitted between January 2002 and January 2021. General demographics, laboratory data, echocardiography findings, and long-term outcomes were analyzed for confirmed viral etiology and unconfirmed etiology groups.The overall hospital survival rate was 54.5%. The age, sex, severity of the hemodynamic condition, and cardiac rhythm were similar between the two groups. Multivariate Cox regression analysis revealed that a confirmed viral etiology (HR 4.201, 95% CI 1.061-16.666), peri-ECMO renal replacement therapy (RRT) (HR 9.804, 1.140-83.333) and a high positive end-expiratory pressure (PEEP) in the ventilator settings at 24 h after ECMO (HR 1.479, 1.020-2.143) were significant prognostic factors for in-hospital mortality. Peri-ECMO RRT was also a significant negative prognostic factor for successful ECMO weaning (OR 0.061, 0.006-0.600) in the multivariate logistic model.Among AFM patients receiving ECMO support, RRT use was associated with a decreased chance of survival to ECMO weaning. Multiple organ dysfunction and a high PEEP were also predictive of a lower chance of hospital survival. Those with a confirmed diagnosis of viral myocarditis may require more medical attention due to the higher risk of hospital mortality than those without a definite diagnosis.

The enhancement of photosynthesis of tea leaves can increase tea yield. In order to explore the regulation mechanism of exogenous melatonin (MT) on the photosynthetic characteristics of tea plants, tea variety ‘Zhongcha 108’ was used as the experimental material in this study. The effects of different concentrations (0, 0.2, 0.3, 0.4 mM) of melatonin on the chlorophyll (Chl) content, stomatal opening, photosynthetic and fluorescence parameters, antioxidant enzyme activity, and related gene expression of tea plants were detected and analyzed. The results showed that under 0.2-mM MT treatment, chlorophyll (Chl) content, photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) improved, accompanied by a decrease in stomata density and increase in stomata area. Zero point two millimolar MT increased Chl fluorescence level and superoxide dismutase (SOD) activity, and reduced hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents, indicating that MT alleviated PSII inhibition and improved photochemical efficiency. At the same time, 0.2 mM MT induced the expression of genes involved in photosynthesis and chlorophyll metabolism to varying degrees. The study demonstrated that MT can effectively enhance the photosynthetic capacity of tea plants in a dose-dependent manner. These results may promote a comprehensive understanding of the potential regulatory mechanism of exogenous MT on photosynthesis in tea plants.

Objective: To investigate the effect of auricular acupuncture on postoperative pain and gastrointestinal motility recovery after laparoscopic surgery for colorectal cancer. Methods: The clinical data of patients who underwent laparoscopic radical surgery for colorectal cancer in our hospital from April 2020 to December 2021 were collected. Based on the inclusion and exclusion criteria, 76 patients were included in the retrospective analysis. Depending on whether they received auricular acupuncture or not, the patients were divided into two groups: 46 patients in the experimental group (auricular acupuncture) and 30 patients in the control group. The differences between the two groups were analyzed. Results: The time to first flatus of the experimental group was significantly shorter than that of the control group (52.2 ± 7.36 h versus 66.3 ± 7.83 h; P < 0.001). Similarly, the time to first defecation of the experimental group was significantly shorter than that of the control group (76.3 ± 7.76 h versus 86.1 ± 10.79 h; P < 0.001). The time to first fluid intake of the auricular group was significantly shorter than that of the control group (90.4 ± 8.92 h versus 107.3 ± 9.66 h, P < 0.001). Compared with the control group, the experimental group scored significantly lower on the visual analogue scale on postoperative days 2 and 3 (P < 0.001). Conclusion: Auricular acupuncture is an effective traditional Chinese medicine external treatment method. It can promote gastrointestinal motility recovery in patients after laparoscopic radical surgery for colorectal cancer and also reduce postoperative pain and discomfort. Furthermore, this therapy is easy to operate and well-accepted by patients. Therefore, it should be strongly promoted in clinical practice.

Myocardial injury resulting from sepsis is the leading cause of death worldwide. Micro RNA miR-122-5p is involved in various physiological and pathological processes and is highly expressed in the heart of septic rats. However, its function in sepsis-caused myocardial injury remains elusive. Herein, a rat model of septic myocardial injury was established by intraperitoneal injection of lipopolysaccharide (LPS), and cardiomyocyte H9c2 was exposed to LPS to induce sepsis-related inflammatory injury in vitro. Inhibition of miR-122-5p suppressed LPS-triggered myocardial injury evidenced by decreased heart weight index (HWI), reduced inflammatory cell infiltration and cell rupture, and reduced cardiac marker enzymes cTnI and LDH. MiR-122-5p inhibition inhibited ROS production and enhanced the activities of antioxidant enzymes CAT, SOD and GSH-px in LPS-treated rats and H9c2 cells. MiR-122-5p inhibition reduced the production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β, and inhibited cell apoptosis along with decreased cleaved-caspase 3 induced by LPS. Moreover, increased GIT1 expression was found following miR-122-5p inhibition. We further verified GIT1 as a target of miR-122-5p, and silencing GIT1 partially reversed the benefits of miR-122-5p loss in LPS-injured H9c2 cells. The HO-1 and NQO-1 expression and Nrf-2 activation were enhanced by miR-122-5p inhibition, which was reversed by GIT1 depletion, indicating the involvement of Nrf-2/HO-1 signaling in regulating miR-122-5p/GIT1-mediated cardioprotection. Taken together, our data suggest that inhibition of miR-122-5p may mitigate sepsis-triggered myocardial injury through inhibiting inflammation, oxidative stress and apoptosis via targeting GIT1, which provides a possible therapeutic target for sepsis., GRAPHICAL ABSTRACT

Objective: To observe the changes of blood gas and serum indexes in patients with acute heart failure complicated with respiratory failure treated by noninvasive ventilator-assisted ventilation. Methods: The records of patients with acute heart failure and respiratory failure, treated in our hospital from June 2019 to June 2021, were selected and stratified based on the received therapy. Of a total of 168 patients, 81 received continuous low flow oxygen therapy (control group) and 87 received noninvasive ventilator (NIV)-assisted ventilation therapy (NIV group). The blood gas and serum indexes of the two groups were compared and analyzed. Results: After 48 hours of treatment, the blood oxygen saturation (SaO2), arterial partial pressure of oxygen (PaO2) and oxygenation index (PaO2/FiO2) in patients in the NIV group were higher than those in the control group, while the expression of arterial partial pressure of carbon dioxide (PaCO2) was lower than that in the control group (P

The high-pressure homogenization (HPH) was used as a post-treatment after acid hydrolysis to alter the morphology and physical properties of ginkgo seed shells cellulose and the resulting nanocellulose were applied to stabilize O/W Pickering emulsions. The length of nanocellulose decreased from 1500 nm to 406 nm with the increasing of homogenization pressure from 10 to 70 MPa. The shorter nanocellulose exhibited higher hydrophobicity and was beneficial for reducing interfacial tension between oil and water. The suspension of longer nanocellulose exhibited a fluid gel behavior. The length of nanocellulose affected the surface coverage ratio of emulsions, which long nanocellulose leaded to a low coverage ratio and short nanocellulose caused a high coverage ratio. Emulsions containing oil phase ranging from 10 to 70% (v/v) could be prepared by only small amounts of nanocellulose treated by 50 MPa (C-50). In addition, the emulsions showed benign stability against a wide range of temperature, pH, and ionic strength environments. The results indicated C-50 not only has the similar amphipathic properties as the cellulose nanocrystals, but also has a relatively long size, showing the property of being as entangled with each other as cellulose nanofibers to form a network structure.

Eleven previously undescribed alkaloids, named sinometumines A-K, along with three known alkaloids, were isolated from the rhizomes of Sinomenium acutum. The chemical structures of these unreported compounds were established using extensive spectroscopic methods (IR, UV, HRESIMS, and NMR), and their absolute configurations were determined by single crystal X-ray diffraction analyses and calculated electronic circular dichroism spectroscopy (ECD). Sinometumine D was the first aporphine-type derived alkaloid inner salt with a rearranged dibenzofuran ring backbone. Sinometumine E was a rare protoberberine-type alkaloid with a complex 6/6/6/6/6/6 hexacyclic skeleton. This was the first report of alkaloids with these two skeletons isolated from S. acutum. All isolates were evaluated for their inhibitory activities against indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO). Lysicamine possessed noteworthy inhibitory activities as an IDO1/TDO dual inhibitor with IC

Rapid volatile detection methods for seed vigour rely heavily on artificial ageing (AA), however the comparability of volatile organic compounds (VOCs) to natural ageing (NA) and practicability of the detection models were not well known. In this study, VOCs between AA and NA sweet corn seeds were compared and Partial Least Squares Regression (PLS-R) models were constructed based on AA to predict the seed vigour of NA. A total of 33 VOCs were identified, among which aldehydes showed the highest consistency between NA and AA. Furthermore, a AS-PLS-R model with variable importance in projection (VIP > 1) and Pearson Correlation Coefficient (r > 0.9) algorithms, which was built on 3 volatile markers: benzaldehyde monomer, n-nonanal, 1-butanol monomer, achieved the best performance (R2p of 0.901 and RMSEP of 0.050). Therefore, coupling Gas Chromatography- Ion Mobility Spectrometry (GC-IMS) with chemometrics can be an effective way to monitor and predict stored seeds vigour.

Background For patients with gastro-oesophageal reflux symptoms, the preferred treatment is proton pump inhibitor (PPI) administration for approximately 8 weeks. However, long-term use of PPIs can cause gut microbiome (GM) disturbances. This study is designed to evaluate the effect of probiotics combined with a PPI on the GM and gastrointestinal symptoms of patients with gastro-oesophageal reflux disease (GERD). Method This is a randomized, double-blind, placebo-controlled trial. A total of 120 eligible patients with GERD will be randomized into the experimental group or the control group. The treatment includes two phases: the initial treatment period lasts 8 weeks (weeks 1–8), and the maintenance treatment period lasts 4 weeks (weeks 9–12). During the initial treatment period, the experimental group will take rabeprazole and LiHuo probiotics, and the control group will take rabeprazole and a probiotic placebo; during the maintenance treatment period, the experimental group will take LiHuo probiotics, and the control group will take a probiotic placebo. The primary measure is the change in the GM. The secondary measures are the Reflux Disease Questionnaire (RDQ) score, Gastrointestinal Symptom Rating Scale (GSRS) score, faecal metabolome (FM), body mass index, Los Angeles grade of oesophagitis, adverse event (AE) rate and treatment compliance. Each outcome indicator will be assessed at day 0 (before administration), day 28 and/or 56 (during administration), and day 84 (end of administration) to reveal intragroup differences. AEs will be monitored to assess the safety of LiHuo probiotics. Discussion This will be the first trial to use the intestinal flora metagene method to analyse the effects of probiotics on patients with GERD receiving long-term PPI treatment. The goal is to provide evidence for the use of probiotics to reduce intestinal flora disorders and other symptoms of gastrointestinal discomfort in patients with GERD who have used PPIs for a long period. Trial registration Chinese Clinical Trial Registry (ChiCTR) (NO. ChiCTR2000038409). Registered on November 22, 2020, http://www.chictr.org.cn/showproj.aspx?proj=56358.

Purpose: Currently, formalin-fixed paraffin-embedded (FFPE) tissue specimens are the conventional material for gene testing for non-small cell lung cancer (NSCLC) patients. In our study, we aimed to develop a quick gene testing procedure using fresh core needle biopsy samples from NSCLC patients.Methods: In total, 77 fresh NSCLC samples obtained from core needle biopsy were evaluated by frozen section examination. If the NSCLC diagnosis and adequate tumor cell counts were confirmed by histopathology, the fresh tissues were used to extract DNA and subsequent gene testing by ARMS-PCR. Meanwhile, the paired FFPE core needle biopsy samples from 30 NSCLC patients also underwent gene testing.Results: In total, 77 fresh samples showed an EGFR mutation rate of 61.0%, higher than the levels in the Asian. Following a comparison of gene testing results with fresh tissues and paired FFPE tissues from the 30 patients, no significant difference in the DNA concentration extracted from fresh tissues and FFPE tissues was found. However, DNA purity was significantly higher in fresh tissues than that in FFPE tissues. Gene testing detected the same gene mutations in 93.3% of cases in fresh tissues and paired FFPE tissues. The gene testing procedure using fresh biopsy samples greatly shortens the waiting time of patients.Conclusion: The multi-gene mutation testing using fresh core needle biopsy samples from NSCLC patients is a reasonable, achievable, and quick approach. Fresh tissues may serve as a potential alternative to FFPE tissues for gene testing in NSCLC patients.

Human immunodeficiency virus (HIV)-Mycobacterium tuberculosis (MTB) co-infection has become a pressing global public health problem. Although tuberculosis (TB) is both treatable and curable, it has been exacerbated by the HIV/acquired immune deficiency syndrome (AIDS) epidemic. HIV-MTB co-infected patients have a variety of disease-specific, and treatment-related factors that can adversely affect their treatment outcomes. This study was conducted to assess the outcomes of TB treatment and its associated factors among HIV-MTB co-infected patients in Sichuan, Southwest China. A retrospective study was performed on HIV-MTB co-infected patients who were diagnosed and registered in TB designated hospitals in Sichuan from January 1, 2016, to December 31, 2020. Data were collected from patients' electronic medical records regarding their demographic, clinical, and social support information, and categorical data, such as sex, were reported using numbers and percentages. χ2 and t-tests were conducted to compare groups in relation to different levels of medical institutions. A binary logistic regression model was used to identify the factors associated with unsuccessful TB treatment outcomes. For logistic regression analysis performed using an α of 0.05, odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for various risk factors. A total of 3677 registered HIV-MTB co-infected patients were enrolled. After adjusting for other variables, male, advanced age, receiving TB treatment at the municipal medical institution, being diagnosed with external pulmonary TB, referral or tracing, being sputum smear positive, not initiating antiretroviral therapy (ART) and not using fixed-dose combinations were the main risk factors for treatment failure of HIV-MTB co-infected patients in Sichuan province. Sex, age, hospital level, patient source, other diagnostic factors (e.g., sputum smear results, anatomical site of TB), and factors of therapeutic schemes (e.g., antiretroviral therapy, fixed-dose combinations) may serve as risk factors to estimate the likely treatment outcome of HIV-TB co-infection.

Background: Patients with long-term insomnia generally experience anxiety and depression. Traditional sleeping pills and anti-anxiety drugs have certain limitations. Xiao Yao San (XYS), a complementary and alternative therapy, has been widely used to treat insomnia combined with anxiety. This study aims to evaluate the efficacy and safety of XYS in the treatment of insomnia combined with anxiety. Methods: Related literature was retrieved from 8 electronic databases from the establishment time to March 2021. The subjects were diagnosed with insomnia combined with anxiety. We assessed the methodological quality of randomized controlled trials (RCTs) according to the Cochrane Handbook. Data analysis was conducted using RevMan 5.3 software. Results: The analysis includes 9 RCTs involving 681 patients. Meta-analysis supported that as an auxiliary drug for Western medicine (WM), XYS could enhance the clinical efficacy of insomnia calculated according to the traditional Chinese medicine (TCM) syndrome score scale (risk ratio [RR]: 1.26; 95% confidence interval [CI]: 1.13–1.43; P = .0002) and reduced the scores of Hamilton Anxiety Scale (mean difference [MD]: −5.19; 95% CI: −7.78 to −2.60; P

Oxidative stress in plants caused by UV-B stress has always been a great challenge to the yield of agricultural products. Carbon dots (CDs) with enzyme-like activity have been developed, and inhibiting oxidative stress in animals has been achieved, but little is known about abiotic stress resistance in plants, especially UV-B stress. In this study, CDs were synthesized from Scutellaria baicalensis via a hydrothermal method. The ability of CDs to scavenge reactive oxygen species (ROS) in vivo and in vitro and to enhance antioxidant resistance in vivo was evaluated. The results show that CDs promoted the nutrient assimilation ability of lettuce seedlings and protected the plants from UV-B stress by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione reductase (GR), and ascorbate peroxidase (APX). Moreover, the antioxidant metabolism of plants can be activated by CDs and the expression levels of aquaporin (AQP) genes PIP1 and PIP2 are also up-regulated. These results facilitate the design and fabrication of CDs to meet the challenge of abiotic stress in food production.

Terrein is a small-molecule polyketide compound with a simple structure mainly isolated from fungi. Since its discovery in 1935, many scholars have conducted a series of research on its structure identification, isolation source, production increase, synthesis and biological activity. Studies have shown that terrein has a variety of biological activities, not only can inhibit melanin production and epidermal hyperplasia, but also has anti-cancer, anti-inflammatory, anti-angiopoietic secretion, antibacterial, insecticidal activities, and so on. It has potential application prospects in beauty, medicine, agriculture and other fields. This article reviews the process of structural identification of terrein since 1935, and summarizes the latest advances in its isolation, source, production increase, synthesis, and biological activity evaluation, with a view to providing a reference and helping for the in-depth research of terrein.

The aroma stability of fresh coffee brew was investigated during storage over 60 minutes, there was a substantial reduction in available 2-furfurylthiol (2-FFT) (84%), methanethiol (72%), 3-methyl-1H-pyrole (68%) and an increase of 2-pentylfuran (65%). It is proposed that 2-FFT was reduced through reversible chemical binding and irreversible losses. Bound 2-FFT was released after cysteine addition, thereby demonstrating that a reversible binding reaction was the dominant mechanism of 2-FFT loss in natural coffee brew. The reduction in available 2-FFT was investigated at different pH and temperatures. At high pH, the reversible binding of 2-FFT was shown to protect 2-FFT from irreversible losses, while irreversible losses led to the reduction of total 2-FFT at low pH. A model reaction system was developed and a potential conjugate, hydroxyhydroquinone, was reacted with 2-FFT. Hydroxyhydroquinone also showed 2-FFT was released after cysteine addition at high pH.

The changes of free and bound volatile compounds in Rubus corchorifolius fruit during ripening were determined with a headspace SPME-GC-MS method. The results suggest that the free aldehydes, alcohols, esters and phenols increases, while that of free terpenoids decreases, with the ripening of the fruit. The bound aldehydes, alcohols, terpenoids, esters and phenols gradually decreases during ripening because these bound compounds are hydrolyzed to their free form. The characteristic free aroma compounds of ripened red fruit were found to be hexanal, 2-heptanone, ethyl hexanoate, 4-terpineol, geranial and methyleugenol. The free aroma compounds in red and yellow fruits exhibit similar odor profiles, and both of them are much sweeter, more floral and greener than the green fruit. The overall aroma of the fruits all ripening stages are mainly attributed to the free aroma compounds including β-damascenone, hexanal, 2-hexenal and linalool. The formation mechanisms of some volatile compounds were proposed.

© 2018 Elsevier Ltd This study attempted to improve Robusta sensory properties by modifying the beans chemical composition. Building on our previous work, which modified bean pH through acid pre-treatment, a model system was developed where, sugar solutions (glucose, fructose, sucrose) were used to pre-treat Robusta coffee beans with the aim to modify the concentration/availability/location of these aroma precursors. Beans were then dried to equal water activity, subjected to equal roast intensity and ground to comparable particle size distributions. The treatment significantly impacted aroma generation during roasting leading to an altered level of pyrazines, furans, ketones, organic acid and heterocyclic nitrogen-containing compounds (p < 0.05). The optimum treatment was 15 g/100 g fructose. 80% treated Robusta could be blended with Arabica in coffee brew without significant aroma differences being perceived when compared to 100% Arabica brew. Furthermore the aroma of the fructose treated Robusta was more stable than Arabica over six weeks accelerated shelflife storage.

Capsaicin increases saliva production, but the impact of this additional saliva on the food matrix is unknown. This study aimed to explain the impact of capsaicin on saliva properties and in-vivo release of 14 aroma compounds in aqueous [aqu] and oil systems [oil]. To investigate the physicochemical effect from diverse properties of aroma compounds, one healthy subject participated in all the sessions to minimise large variations between individuals. Capsaicin enhanced saliva flow rate (by 172% [aqu] and 85% [oil]) and salivary protein concentration (by 142% [aqu] and 149% [oil]). Furthermore, capsaicin-in-oil stimulated saliva formed a more stable emulsion in the mouth (17% higher zeta-potential and 15% smaller particle size). In-nose release concentrations measured by APCI-MS for certain esters were reduced by capsaicin (e.g., isoamyl acetate was reduced by 65% [aqu] and 76% [oil]), which suggests that capsaicin may induce stronger oral interactions between specific aroma compounds and salivary proteins.

Although low circulating levels of the vitamin A metabolite, all-trans retinoic acid (ATRA), are associated with increased risk of cardiovascular events and all-cause mortality, few studies have addressed whether cardiac retinoid levels are altered in the failing heart. Here, we showed that proteomic analyses of human and guinea pig heart failure (HF) were consistent with a decline in resident cardiac ATRA. Quantitation of the retinoids in ventricular myocardium by mass spectrometry revealed 32% and 39% ATRA decreases in guinea pig HF and in patients with idiopathic dilated cardiomyopathy (IDCM), respectively, despite ample reserves of cardiac vitamin A. ATRA (2 mg/kg/d) was sufficient to mitigate cardiac remodeling and prevent functional decline in guinea pig HF. Although cardiac ATRA declined in guinea pig HF and human IDCM, levels of certain retinoid metabolic enzymes diverged. Specifically, high expression of the ATRA-catabolizing enzyme, CYP26A1, in human IDCM could dampen prospects for an ATRA-based therapy. Pertinently, a pan-CYP26 inhibitor, talarozole, blunted the impact of phenylephrine on ATRA decline and hypertrophy in neonatal rat ventricular myocytes. Taken together, we submit that low cardiac ATRA attenuates the expression of critical ATRA-dependent gene programs in HF and that strategies to normalize ATRA metabolism, like CYP26 inhibition, may have therapeutic potential.

Although all cancers are molecularly distinct, many share common driver mutations. Pan-cancer analysis, utilizes next-generation sequencing (NGS), pan-cancer model systems, and pan-cancer projects such as The Cancer Genome Atlas (TCGA), to assess frequently mutated genes and other genomic abnormalities that are common among many cancer types, regardless of the tumor origin, providing new directions for tumor biology research. However, there is currently no study that has objectively analyzed the results of pan-cancer studies on cancer biology. For this study, 999 articles on pan-cancer published from 2006 to 2020 were obtained from the Scopus database, and bibliometric methods were used to analyze citations, international cooperation, co-authorship and keyword co-occurrence clusters. Furthermore, we also focused on and summarized the application of pan-cancer in breast cancer. Our result shows that the pan-cancer studies were first published in 2006 and entered a period of rapid development after 2013. So far, 86 countries have carried out international cooperation in sharing research. Researchers form the United States and Canada have published the most articles and have made the most extensive contribution to this field, respectively. Through author keyword analysis of the 999 articles, TCGA, biomarkers, NGS, immunotherapy, DNA methylation, prognosis, and several other keywords appear frequently, and these terms are hot spots in pan-cancer studies. There are four subtypes of breast cancer (luminalA, luminalB, HER2, and basal-like) according to pan-cancer analysis of breast cancer. Meanwhile, it was found that breast cancer has genetic similarity to pan-gynecological cancers, such as ovarian cancer, which indicates related etiology and possibly similar treatments. Collectively, with the emergence of new detection methods, new cancer databases, and the involvement of more researchers, pan-cancer analyses will play a greater role in cancer biology research.

Melatonin (MT) is a bioactive molecule that can regulate various developmental processes. Changes in lignin content play important roles in plant growth and development. Herein, quantitative analysis and histochemical staining showed that lignin content significantly increased over time, and melatonin treatment triggered the lignification at 8 and 16 d in tea leaves. The POD activity participated in lignin formation had also been significantly improved. The effect of melatonin on the increase of lignin content was attenuation over time. Sequencing results based on transcriptome at 8 and 16 d showed that 5273 and 3019 differentially expressed genes (DEGs) were identified in CK1 vs. MT1 and CK2 vs. MT2, respectively. A total of 67 DEGs were annotated to lignin biosynthesis, and 38 and 9 genes were significantly up-regulated under melatonin treatment, respectively. Some transcription factor genes such as MYB were also identified among the two pairwise comparisons, which might relate to lignin metabolism. Melatonin increased the degree of lignification in tea leaves by modifying the enzyme genes expression involved in lignin synthesis pathway. These results provide a reference for further study on the molecular mechanism of the dynamic changes of lignin content induced by melatonin treatment in tea plants.

Takifugu rubripes is well-known for its unique flavour but can also develop a putrid off-note. To eliminate off-note and promote desirable flavour, four cooking processes (boiling, steaming, microwave-heating and roasting) were explored to determine their effects on cooked T. rubripes. The temperature and water dynamics, physico-chemical properties were analysed and correlated with sensory qualities. The changes of centre temperature dynamics during cooking decreased the water mobility and led to varied sensory properties. Six out of ten orthonasal aroma attributes and four out of five mouthfeel attributes were significantly different among samples (p < 0.05). Based on partial least squares regression analysis, orthonasal aroma attributes “roasted” and “earthy/putrid fish” highly correlated with the volatile compounds generated from Maillard reaction and lipid oxidation, respectively; meanwhile mouthfeel attributes of chewy/fibre and tender/juicy were highly associated with water loss and moisture, respectively. This study provides insights for optimising cooking conditions to create desirable fish flavour.

Aroma compounds are diverse low molecular weight organic molecules responsible for the flavour of food, medicines or cosmetics. Natural and artificial aroma compounds are manufactured and used by the industry to enhance the flavour and fragrance of products. While the low concentrations of aroma compounds present in food may leave no effect on the structural integrity of the mucosa, the effect of concentrated aroma volatiles is not well understood. At high concentrations, like those found in some flavoured products such as e-cigarettes, some aroma compounds are suggested to elicit a certain degree of change in the mucin glycoprotein network, depending on their functional group. These effects are particularly associated with carbonyl compounds such as aldehydes and ketones, but also phenols which may interact with mucin and other glycoproteins through other interaction mechanisms. This study demonstrates the formation of such interactions in vitro through the use of molecular hydrodynamics. Sedimentation velocity studies reveal that the strength of the carbonyl compound interaction is influenced by compound hydrophobicity, in which the more reactive short chain compounds show the largest increase in mucin-aroma sedimentation coefficients. By contrast, the presence of groups that increases the steric hindrance of the carbonyl group, such as ketones, produced a milder effect. The interaction effects were further demonstrated for hexanal using size exclusion chromatography light scattering (SEC-MALS) and intrinsic viscosity. In addition, phenolic aroma compounds were identified to reduce the sedimentation coefficient of mucin, which is consistent with interactions in the non-glycosylated mucin region.

Background and Aims The main cause of sepsis-induced Acute kidney injury (AKI) is acute infection after surgery and subsequent progression. However, the mechanism by which AKI is caused and developed from sepsis are not completely known. Herein, we determined the role of CCAAT/enhancer-binding protein β (C/EBP β) in sepsis-induced AKI Methods C/EBP β expression was up or down-regulated in LPS-stimulated human renal tubular epithelial cells in vitro by recombinant adenoviruses or siRNA. Subsequent analyses included the test of TNF-α and IL-6 levels by ELISA, cell cycle assay by flow cytometry. Results C/EBP β was aberrantly expressed in renal tubular epithelial HK-2 cells exposed to LPS. C/EBP β overexpression significantly enhanced, but C/EBP β silencing obviously decreased the production and secretion of inflammatory cytokines TNF-α and IL-6 induced by LPS stimulus in HK-2 cells. And the cell cycle arrest of HK-2 cells induced by LPS was also enhanced after C/EBP β overexpression while attenuated after C/EBP β silencing. Consistent pattern of changes in Cyclin D1 and p21 expression were observed in LPS-stimulated HK-2 cells after C/EBP β silencing and C/EBP β overexpression. Additionally, the increased p-NF-κB levels induced by LPS were found to be obviously decreased after C/EBP β silencing in HK-2 cells. And the enhanced TNF-α and IL-6 secretion as well as cell cycle arrest by C/EBP β overexpression were blocked by BAY11-7082 inhibitor of NF-κB pathway. Conclusions C/EBP β could mediate the LPS-induced aberrant inflammatory response and cell cycle arrest in tubular epithelial cells by NF-κB pathway.

SuHeXiang (SHX) has been used to treat a wide range of diseases, including those related to the central nervous system. However, the effects of SHX on mood disorders are still elusive. This study aimed to investigate the effects of SHX essential oil on stress-induced depression of mice. In an acute stress-induced depression model, mice inhaled vehicle (1% Tween 80) for 10 min or 10% SHX for 10 or 30 min once daily for 12 continuous days. In the chronic mild stress (CMS)-induced depression model, mice were exposed to a 28-d CMS treatment. Tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and novelty suppressed feeding (NSF) test were conducted. In addition, serum levels of angiogenin (ANG), thrombopoietin (TPO), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA) assays. The results showed that in mice exposed to acute stress, repeated SHX inhalation exerted significant antidepressant and anxiolytic activities, and also reduced the serum levels of ANG, TPO, IL-6, and TNF-α. It also significantly reversed the depressive and anxiety-like behaviors, and reduced the serum levels of ANG and TPO in mice exposed to CMS. This is the first report to show that SHX inhalation could produce significant antidepressant and anxiolytic-like effects. These effects might be mediated by SHX ability to modulate the inflammatory response, and reduce dysfunction of vascular genesis and thrombosis. These results support further exploration for developing SHX inhalation as a novel therapeutic strategy for depression and stress-related disorders.

Six previously undescribed oleanane-type triterpenoid saponins, fortunosides A–F, together with six known ones, were isolated from the aerial parts of Lysimachia fortunei Maxim. Their structures were established by spectroscopic data analyses (1D, 2D-NMR and HRESIMS) and chemical methods. All isolated triterpenoid saponins were evaluated for their cytotoxicity against four human liver cancer cell lines (SMMC-7721, Hep3B, HuH7, and SK-Hep-1). Three saponins with the aglycone protoprimulagenin A exhibited moderate cytotoxicity against all of the tested human cancer cell lines, with IC50 values ranging from 4.76 to 15.12 μM.

Nitrogen oxide (NOx) is produced during combustion at high temperature, which is a major constituent of air pollutants. Recent studies suggested inconsistent results on the association between NOx exposure and cardiovascular-related malformations. We aimed to assess aforementioned association in pregnant women in the first trimester and cardiovascular-related malformations of infants. A systematic literature review identified studies for observational studies about NOx exposure and cardiovascular-related malformation in PubMed. Random-effect models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned association. Finally, nine studies met the inclusion criteria. Overall, the SOR of cardiovascular-related malformation per 10 ppb increment in NOx and NO2 concentration was 1.01 (95% CI: 0.98–1.04; I2 = 38.6%, P=0.09) and 0.99 (95% CI: 0.95–1.04; I2 = 37.8%, P=0.13), respectively. Stratifying by study design, geographic locations, and confounded adjustments, the majority of strata showed negative results, which were consistent with the main findings. However, we found that exposure to NOx and NO2 in the first trimester increased the risk of coarctation of the aorta (COA) malformation by 13% and 19%, respectively. Our study provided limited evidence regarding the association between NOx exposure in the first trimester and cardiovascular-related malformations in infants.

Background Coronavirus disease 2019 (COVID-19) has evolved into a worldwide pandemic, and has been found to be closely associated with mental and neurological disorders. We aimed to comprehensively quantify the association between mental and neurological disorders, both pre-existing and subsequent, and the risk of susceptibility, severity and mortality of COVID-19. Methods In this systematic review and meta-analysis, we searched PubMed, Web of Science, Embase, PsycINFO, and Cochrane library databases for studies published from the inception up to January 16, 2021 and updated at July 7, 2021. Observational studies including cohort and case-control, cross-sectional studies and case series that reported risk estimates of the association between mental or neurological disorders and COVID-19 susceptibility, illness severity and mortality were included. Two researchers independently extracted data and conducted the quality assessment. Based on I2 heterogeneity, we used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (95% CI). Subgroup analyses and meta-regression analysis were also performed. This study was registered on PROSPERO (registration number: CRD 42021230832). Finding A total of 149 studies (227,351,954 participants, 89,235,737 COVID-19 patients) were included in this analysis, in which 27 reported morbidity (132,727,798), 56 reported illness severity (83,097,968) and 115 reported mortality (88,878,662). Overall, mental and neurological disorders were associated with a significant high risk of infection (pre-existing mental: OR 1·67, 95% CI 1·12-2·49; and pre-existing neurological: 2·05, 1·58-2·67), illness severity (mental: pre-existing, 1·40, 1·25-1·57; sequelae, 4·85, 2·53-9·32; neurological: pre-existing, 1·43, 1·09-1·88; sequelae, 2·17, 1·45-3·24), and mortality (mental: pre-existing, 1·47, 1·26-1·72; neurological: pre-existing, 2·08, 1·61-2·69; sequelae, 2·03, 1·66-2·49) from COVID-19. Subgroup analysis revealed that association with illness severity was stronger among younger COVID-19 patients, and those with subsequent mental disorders, living in low- and middle-income regions. Younger patients with mental and neurological disorders were associated with higher mortality than elders. For type-specific mental disorders, susceptibility to contracting COVID-19 was associated with pre-existing mood disorders, anxiety, and attention-deficit hyperactivity disorder (ADHD); illness severity was associated with both pre-existing and subsequent mood disorders as well as sleep disturbance; and mortality was associated with pre-existing schizophrenia. For neurological disorders, susceptibility was associated with pre-existing dementia; both severity and mortality were associated with subsequent delirium and altered mental status; besides, mortality was associated with pre-existing and subsequent dementia and multiple specific neurological diseases. Heterogeneities were substantial across studies in most analysis. Interpretation The findings show an important role of mental and neurological disorders in the context of COVID-19 and provide clues and directions for identifying and protecting vulnerable populations in the pandemic. Early detection and intervention for neurological and mental disorders are urgently needed to control morbidity and mortality induced by the COVID-19 pandemic. However, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. More studies are needed to explore long-term mental and neurological sequela, as well as the underlying brain mechanisms for the sake of elucidating the causal pathways for these associations. Funding This study is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, Special Research Fund of PKUHSC for Prevention and Control of COVID-19, and the Fundamental Research Funds for the Central Universities.

In the present study, two different rat models of sepsis, cecal ligation and puncture (CLP), and lipopolysaccharide (LPS), were established. Changes in autophagy in both models were compared using transmission electron microscopy (TEM), immunohistochemistry, western blotting, and quantitative polymerase chain reaction techniques. Consequently, TEM analysis revealed autophagic bodies in the CLP and LPS sepsis models. In addition, autophagy-related protein LC3 A-specific staining was detected in the cytoplasm. However, analysis of protein and gene expression levels revealed a statistically significant increase in autophagic activity 12 and 24 h following induction of the CLP group, and 2 h following induction of the LPS group. Thus, it was concluded that both models of sepsis exhibited increased autophagic activity of the cardiomyocytes over time. The LPS model was superior to the CLP model in perturbation of molecular biological mechanisms, while the latter would be more likely suited for the study of physiological functions.

The kinetics of browning and the correlation between browning products (BPs) and pyrazine compounds were investigated by heating equimolar l-ascorbic acid (ASA)/acidic amino acids under weak alkaline conditions at 120-150°C for 10-120min. The formations of BPs and pyrazine compounds from the reaction were monitored by UV-vis and SPME-GC-FID, respectively. The formation of BPs in both ASA/l-glutamic acid and ASA/l-aspartic acid model reaction systems followed zero order reaction kinetics with activation energies (Ea) of 90.13 and 93.38kJ/mol, respectively. ASA/l-aspartic acid browned at a slightly higher rate than ASA/l-glutamic acid. The total concentration of pyrazine compounds was highly and positively correlated with that of BPs. Based on the observed kinetic data, the formation mechanisms of BPs and pyrazine compounds were proposed.