Characterization of the key flavor compounds in cream cheese by GC-MS, GC-IMS, sensory analysis and multivariable statistics.

The aroma types of cream cheese affect its commercial value and consumer acceptability. However, the types of volatile substances and sensory characteristics of cream cheese at different fermentation stages are still unclear. Therefore, in this study, headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) were used to analyze the volatile substances in cream cheese fermentation. Orthogonal partial least squares discriminant analysis (OPLS-DA), odor activity value (OAV), relative odor activity value (ROAV) and variable projection importance (VIP) were used to identify the characteristic flavor substances in cream cheese fermentation. Finally, the relationship between key flavor substances and sensory characteristics was determined by partial least squares (PLS) analysis. A total of 34 and 36 volatile organic compounds were identified by HS-SPME-GC-MS and HS-GC-MS, respectively, and 14 characteristic flavor substances were found, based on VIP, ROAV and OAV models. Combined with sensory analysis and flavor substance changes, it was found that the cream cheese fermented for 15 d had the best flavor and taste. This study reveals the characteristics and contribution of volatile substances in cream cheese at different fermentation stages, which provides new insights into improving flavor and quality control.

Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

Electromagnetic-acoustic splitter with a tunable splitting ratio based on copper plates.

Acoustic splitters and electromagnetic splitters can be applied in various fields (e.g., navigation and interference detection). However, there is still a lack of study of structures that can simultaneously split acoustic and electromagnetic beams. In this study, a novel, to the best of our knowledge, electromagnetic-acoustic splitter (EAS) based on copper plates is proposed, which can simultaneously produce identical beam-splitting effects for transverse magnetic (TM)-polarized electromagnetic and acoustic waves. Different from previous beam splitters, the beam splitting ratio of the proposed passive EAS can be simply tuned by changing the incident angle of the input beam, i.e., a tunable splitting ratio can be achieved without additional energy consumption. The simulated results verify that the proposed EAS can create two transmitted split beams with a tunable splitting ratio for both electromagnetic and acoustic waves. This may have applications in dual-field navigation/detection, which can provide additional information and higher accuracy compared with single-field navigation/detection.

Characterization of a fermented dairy, sour cream: Lipolysis and the release profile of flavor compounds.

Lipolysis and flavor development during fermentation of sour cream were studied by evaluating the physicochemical changes, sensory differences and volatile components. The fermentation caused significant changes in pH, viable count and sensory evaluation. The peroxide value (POV) decreased after reaching the maximum value of 1.07 meq/kg at 15 h, while thiobarbituric acid reactive substances (TBARS) increased continuously with the accumulation of secondary oxidation products. The Free fatty acids (FFAs) in sour cream were mainly myristic, palmitic and stearic. GC-IMS was used to identify the flavor properties. A total of 31 volatile compounds were identified, among which the contents of characteristic aromatic substances such as ethyl acetate, 1-octen-3-one and hexanoic acid were increased. The results suggest that lipid changes and flavor formation in sour cream are influenced by fermentation time. Furthermore, flavor compounds may be related to lipolysis such as 1-octen-3-one and 2- heptanol were also observed.

Active Thermal Metasurfaces for Remote Heating/Cooling by Mimicking Negative Thermal Conductivity.

Remote temperature control can be obtained by a long-focus thermal lens that can focus heat fluxes into a spot far from the back surface of the lens and create a virtual thermal source/sink in the background material, around which the temperature field distribution can be remotely controlled by varying the parameters of the thermal lens. However, because of the lack of negative thermal conductivity, existing thermal lenses have extremely short focal lengths and cannot be used to remotely control the temperature field around the virtual thermal source/sink. In this study, a general approach is proposed to equivalently realize materials with negative thermal conductivity using elaborately distributed active thermal metasurfaces (ATMSs). Subsequently, the proposed ATMS is used to implement a novel thermal lens with a long focal length designed using transformation thermodynamics, and finally realize the ATMS with realistic materials and experimentally verify the performance of the designed long-focus thermal lens (measured focal length of 19.8 mm) for remote heating/cooling. The proposed method expands the scope of the thermal conductivity and provides new pathways to realize unprecedented thermal effects with effective negative thermal conductivity, such as "thermal surface plasmon polaritons," a thermal superlens, the thermal tunneling effect, and the thermal invisible gateway.

GC-MS and GC×GC-ToF-MS analysis of roasted / broth flavors produced by Maillard reaction system of cysteine-xylose-glutamate.

Maillard reaction products (MRPs) with roasted/broth flavors were prepared and analyzed for the resulting flavor differences. The identification of volatile compounds in MRPs was carried out by GC-MS and GC × GC-ToF-MS. A total of 88 compounds were identified by GC-MS; 130 compounds were identified by GC × GC-ToF-MS, especially acids and ketones were identified. Principal component analysis (PCA) was used to visualize the volatile compounds, and the roasted/broth flavors were differentiated. The contents and types of pyrazines were more in roasted flavors; thiol sulfides and thiophenes were more in broth flavors. All in all, the differences in volatile compounds producing roasted/broth flavors were studied through the cysteine-xylose-glutamate Maillard reaction system, which provided a theoretical basis for the future use of Maillard reaction to simulate meat flavor.

Effects of Reducing Sugars on the Structural and Flavor Properties of the Maillard Reaction Products of Lycium barbarum Seed Meal.

Lycium barbarum seed meal contains a variety of bioactive compounds, but the use of L. barbarum seed meal in the food industry is rare. This study aimed to evaluate the effect of reducing sugars on the structural and flavor properties of the Maillard reaction products (MRPs) of the Lycium barbarum seed meal hydrolysate (LSH). The results showed that the flavors and tastes of the MRPs were affected by reducing sugars. In comparison to oligosaccharides, monosaccharides were more suitable for the development of MRPs with good sensory qualities. The structural characteristics of L. barbarum seed meal precursor MRPs were also affected by reducing sugars. The MRPs produced with the participation of monosaccharides had higher ultraviolet absorption and browning than the MRPs produced with oligosaccharides. The molecular weights of the MRPs were found to be 128-500 Da and 500-1000 Da. Compared to the MRPs made from other sugars, xylose-meridian products (X-MRPs) had a stronger meaty flavor. The mellowness and continuity of the MRPs made from monosaccharides were superior to those made from oligosaccharides. The MRPs formed by L. barbarum seed meal exhibited the characteristics of umami and meat flavor. MRPs with better flavors may be used to develop new types of seasoning salts.

Delayed traumatic purulent pericarditis with cardiac tamponade - A rare case report.

Thoracic trauma often results in immediate or delayed hemorrhage. There are few cases of purulent pericarditis with pericardial tamponade reported in the literature. If a devastating complication develops several weeks following blunt thoracic trauma, the causal relationship with the thoracic trauma event is less evident. As such, accurate diagnosis and subsequent effective treatment implementation is likely to be delayed. Herein, we present the case of a 46-year-old male patient with delayed purulent pericarditis that led to cardiac tamponade 2 weeks after the initial trauma.

Clinical efficacy of sofosbuvir/daclatasvir in patients with COVID-19: a systematic review and meta-analysis of randomized trials.

BACKGROUND: This study investigated the clinical efficacy sofosbuvir/daclatasvir (SOF-DCV) in patients with COVID-19. RESEARCH DESIGN AND METHODS: PubMed, Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before January 6, 2022. Only randomized controlled trials (RCTs) comparing the clinical efficacy of SOF-DCV (study group) with alternative treatments (control group) in patients with COVID-19 were included. RESULTS: A total of 9 RCTs were included. The all-cause mortality rate in the study group was 10.7% (96/898), which was lower than that in the control group (12.3%, 108/871). However, this difference was not statistically significant (odds ratio [OR] = 0.83; 95% CI, 0.62-1.12; I2 = 49%). The overall clinical recovery rate was significantly higher in the study group than in the control group (OR = 2.34; 95% CI, 1.47-3.72; I2 = 20%). Furthermore, the average length of hospital stay was shorter in the study group than in the control group (mean deviation = -1.84; 95% CI, -3.42 to -0.26, I2 = 68%). CONCLUSIONS: Although SOF-DCV did not confer a survival benefit in patients with COVID-19, it may increase a patient's odds of clinical recovery, and shorten the length of their hospital stay.

Gut modulatory effects of flaxseed derived Maillard reaction products in Sprague-Dawley rats during sub-chronic toxicity.

Our study aimed to understand the effects of Maillard reaction products (MRPs) intake on intestinal health, in vitro digestion, and fermentation metabolites in Sprague-Dawley (SD) rats. MRPs promoted the digestion of pepsin, but was not conducive to the subsequent in vitro digestion of trypsin. MRPs ingestion increased the propionate in intestine, but it could not change the branched-chain fatty acids (BCFAs) and short-chain fatty acids (SCFAs). However, MRPs ingestion led to an increase in the Lactobacillus abundance in gut. In the high-dose groups, the abundance of genes in partial amino acid and monosaccharide metabolism increased, while in lipid metabolism decreased compared with the middle dose groups. Therefore, the absorption of MRPs was lowered than that of protein and carbohydrates. Through functional predictive analysis, our study could reveal the effects of long-term intake of MRPs on intestinal health in SD rats.

Efficacy of Prophylactic Traditional Chinese Medicine on Skin Toxicity of Afatinib in EGFR Mutation-Positive Advanced Lung Adenocarcinoma: A Single-Center, Prospective, Double-Blinded, Randomized-Controlled Pilot Trial.

OBJECTIVES: To evaluate the efficacy of prophylactic traditional Chinese medicine (TCM) on skin toxicities in patients with advanced lung adenocarcinoma treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in a randomized-controlled trial (RCT). MATERIALS AND METHODS: This pilot study was a prospective, single-center, double-blinded RCT. The study enrolled patients with a new diagnosis of locally advanced and metastatic lung adenocarcinoma harboring EGFR mutations who were treated with first-line afatinib from July 1, 2016 to December 31, 2017. Thirty patients who met the inclusion and exclusion criteria were assigned to the TCM and placebo groups with simple randomization. TCM and placebo were initiated at the same time as afatinib and were administered for 3 months. The survival of each subject was followed until 3 years. RESULTS: There were 36 patients with newly diagnosed lung adenocarcinoma during the study period. After the exclusion of 6 patients, the remaining 30 patients were assigned to the TCM (n = 14) and placebo (n = 16) groups comprising the intention-to-treat population. The time to first skin toxicity was 22.3 days in the TCM group and 17.6 days in the placebo group (P = .510) in the per-protocol population. The analysis of the present pilot study results determined that the difference in time to first skin toxicity between the 2 groups would reach statistical significance with a sample size of 237 based on a power of 0.8. There were significant differences in certain subscales of quality of life between the TCM and placebo groups; however, there was no significant difference in progression-free survival or overall survival between the 2 groups. CONCLUSIONS: Integrative TCM may prolong the time to first skin toxicity in patients with advanced lung adenocarcinoma treated with first-line afatinib. Prophylactic TCM could delay skin toxicity of any grade and reduce the incidence of grade 3 skin toxicity. Future large-scale RCTs are warranted to validate these findings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05204758. Registered on 24 Jan 2022.

Analysis of key precursor peptides and flavor components of flaxseed derived Maillard reaction products based on iBAQ mass spectrometry and molecular sensory science.

Flaxseed derived Maillard reaction products (MRPs) have typical meaty flavor, but there is no report on comparison of their amino acids and peptides reactivity. The peptides and amino acids of flaxseed protein hydrolysates were separately collected by G-15 gel chromatography. Taste dilution analysis (TDA) showed that peptides-MRPs had high umami, mouthfulness, and continuity enhancement. Further, LC-MS/MS revealed that flaxseed protein hydrolysates consumed 41 peptides after Maillard reaction. Particularly, DLSFIP (Asp-Leu-Ser-Phe-Ile-Pro) and ELPGSP (Glu-Leu-Pro-Gly-Ser-Pro) accounted for 42.22% and 20.41% of total consumption, respectively. Aroma extract dilution analysis (AEDA) indicated that formation of sulfur-containing flavors was dependent on cysteine, while peptides were more reactive than amino acids for nitrogen-containing heterocycles. On the other hand, 11 flavor compounds with flavor dilution (FD) ≥ 64 were identified for flaxseed derived MRPs, such as 2-methylthiophene, 2-methyl-3-furanthiol, furfural, 2-furfurylthiol, 3-thiophenethiol, thieno[3,2-b] thiophene, 2,5-thiophenedicarboxaldehyde, 2-methylthieno[2,3-b] thiophene, 1-(2-methyl-3-furylthio)-ethanethiol, 2-methylthieno[3,2-b] thiophene, and bis(2-methyl-3-furyl)-disulfide. In addition, we further demonstrated the flavors formation mechanism of flaxseed derived MRPs.

Lysosome TMEM175 Potassium Channel Protein and Parkinson’s Disease / 中国生物化学与分子生物学报

Parkinson’s disease (PD)is a complex neurodegenerative disorder by motor impairments and non-motor symptoms. While dopamine-based therapies are effective in fighting the symptoms in the early stages of the disease‚ a lack of neuroprotective drugs means that the disease continues to progress. New disease modifying therapies and novel therapeutic strategies are in high demand for PD patients. Genetic studies indicated that both rare and common genetic variants could induce the development PD. As a risk candidate gene for Parkinson’s disease‚ TMEM175 encodes a lysosomal potassium channel protein with new structures‚ and the protein plays an important role in maintaining lysosomal membrane potential and pH stability. With the in-depth understanding for its structure and function‚ TMEM175 deficiency results in decreased lysosomal catalytic activity and the pathological aggregation of α-synuclein. In view of the importance of lysosome potassium channel TMEM175‚ it could be an interesting target for the development of drugs to treat Parkinson’s disease and other neurodegenerative diseases. Herein we review the structure and function TMEM175‚ and focuses on its involvement in the occurrence and development of PD by affecting the function of lysosome as a homeostatic regulator. Future drug screenings based on lysosome TMEM175 may be carried out to maintain the active state or enhance the expression of TMEM175 to improve the condition of PD patients. Further investigations are needed to study how to maintain the balance between the open and closed state of TMEM175 channels to regulate the ion homeostasis of lysosomes. Studies of this ion channel protein will bring new strategies and ideas for the treatment of PD‚ and provide support for establishing the molecular status of TMEM175 in the diagnosis and treatment of PD.

Facilitated and Controlled Strontium Ranelate Delivery Using GCS-HA Nanocarriers Embedded into PEGDA Coupled with Decortication Driven Spinal Regeneration.

BACKGROUND AND PURPOSE: Strontium ranelate (SrR) is an oral pharmaceutical agent for osteoporosis. In recent years, numerous unwanted side effects of oral SrR have been revealed. Therefore, its clinical administration and applications are limited. Hereby, this study aims to develop, formulate, and characterize an effective SrR carrier system for spinal bone regeneration. METHODS: Herein, glycol chitosan with hyaluronic acid (HA)-based nanoformulation was used to encapsulate SrR nanoparticles (SrRNPs) through electrostatic interaction. Afterward, the poly(ethylene glycol) diacrylate (PEGDA)-based hydrogels were used to encapsulate pre-synthesized SrRNPs (SrRNPs-H). The scanning electron microscope (SEM), TEM, rheometer, Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were used to characterize prepared formulations. The rabbit osteoblast and a rat spinal decortication models were used to evaluate and assess the developed formulation biocompatibility and therapeutic efficacy. RESULTS: In vitro and in vivo studies for cytotoxicity and bone regeneration were conducted. The cell viability test showed that SrRNPs exerted no cytotoxic effects in osteoblast in vitro. Furthermore, in vivo analysis for new bone regeneration mechanism was carried out on rat decortication models. Radiographical and histological analysis suggested a higher level of bone regeneration in the SrRNPs-H-implanted groups than in the other experimental groups. CONCLUSION: Local administration of the newly developed formulated SrR could be a promising alternative therapy to enhance bone regeneration in bone-defect sites in future clinical applications.

A Real-Time Artificial Intelligence-Assisted System to Predict Weaning from Ventilator Immediately after Lung Resection Surgery.

Assessment of risk before lung resection surgery can provide anesthesiologists with information about whether a patient can be weaned from the ventilator immediately after surgery. However, it is difficult for anesthesiologists to perform a complete integrated risk assessment in a time-limited pre-anesthetic clinic. We retrospectively collected the electronic medical records of 709 patients who underwent lung resection between 1 January 2017 and 31 July 2019. We used the obtained data to construct an artificial intelligence (AI) prediction model with seven supervised machine learning algorithms to predict whether patients could be weaned immediately after lung resection surgery. The AI model with Naïve Bayes Classifier algorithm had the best testing result and was therefore used to develop an application to evaluate risk based on patients' previous medical data, to assist anesthesiologists, and to predict patient outcomes in pre-anesthetic clinics. The individualization and digitalization characteristics of this AI application could improve the effectiveness of risk explanations and physician-patient communication to achieve better patient comprehension.

Strontium ranelate-laden near-infrared photothermal-inspired methylcellulose hydrogel for arthritis treatment.

Rheumatoid arthritis (RA) is of foremost concern among long-term autoimmune disorders, as it leads to inflammation, exudates, chondral degeneration, and painful joints. Because RA severity often fluctuates over time, a local drug delivery method that titrates release of therapeutics to arthritis bioactivity should represent a promising paradigm of RA therapy. Given the local nature of RA chronic illnesses, polysaccharide-drug delivering systems have the promise to augment therapeutic outcomes by offering controlled release of bioactive materials, diminishing the required frequency of administration, and preserving therapeutic levels in affected pathological regions. Herein, an intra-articular photothermal-laden injectable methylcellulose (MC) polymeric hydrogel carrier incorporating strontium ranelate (SrR) and sodium chloride was investigated to resolve these issues. Physicochemical and cellular characteristics of the MC carrier system were thoroughly evaluated. The slow release of SrR, enhancement of the material mechanical strength, and the potential of the non-invasive near-infrared photothermal gel to improve blood circulation and suppress inflammation in a mini-surgical model of RA were examined. Biocompatibility and suppression of intracellular ROS-induced inflammation were observed. This multifunctional photothermal MC hydrogel carrier is anticipated to be an alternative approach for future orthopedic disease treatment.

ATAD3A stabilizes GRP78 to suppress ER stress for acquired chemoresistance in colorectal cancer.

AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45+ intratumoral infiltrating lymphocytes (TILs) and memory CD45RO+ TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.

Promotion of Activated Carbon on the Nucleation and Growth Kinetics of Methane Hydrates.

Due to the hybrid effect of physical adsorption and hydration, methane storage capacity in pre-adsorbed water-activated carbon (PW-AC) under hydrate favorable conditions is impressive, and fast nucleation and growth kinetics are also anticipated. Those fantastic natures suggest the PW-AC-based hydrates to be a promising alternative for methane storage and transportation. However, hydrate formation refers to multiscale processes, the nucleation kinetics at molecule scale give rise to macrohydrate formation, and the presence of activated carbon (AC) causes this to be more complicated. Although adequate nucleation sites induced by abundant specific surface area and pore texture were reported to correspond to fast formation kinetics at macroperspective, the micronature behind that is still ambiguous. Here, we evaluated how methane would be adsorbed on PW-AC under hydrate favorable conditions to improve the understanding of hydrate fast nucleation and growth kinetics. Microbulges on AC surface were confirmed to provide numerous nucleation sites, suggesting the contribution of abundant specific surface area of AC to fast hydrate nucleation and growth kinetics. In addition, two-way convection of water and methane molecules in micropores induced by methane physical adsorption further increases gas-liquid contact at molecular scale, which may constitute the nature of confinement effect of nanopore space.

On the influenza vaccination policy through mathematical modeling.

OBJECTIVES: Aimed at mitigating influenza transmission, this study assessed the timing of the vaccination program and took vaccine capacity, strain mismatch and priority group into consideration. METHODS: An age-structured dynamic transmission model was fitted to the laboratory data of the national influenza surveillance system to reconstruct a baseline scenario with which the vaccination scenarios of interest could be compared. Outcome measures were defined as the impacts on the seasonal epidemic: decompression of the epidemic peak, reduction of the epidemic burden and change of the epidemic peak time. RESULTS: It was found that vaccine capacity building, although indispensable, could not guarantee substantial impact on the seasonal influenza epidemic. Vaccine mismatch might greatly offset vaccine capacity building. Notably, advance vaccine distribution could compensate for some vaccine underperformance. In the case of a well-matched vaccine, advance vaccine distribution could even exploit its utility. CONCLUSIONS: This study indicated that timely vaccine distribution should be put high on the agenda of seasonal influenza control policies. It provided a tangible platform for the policymakers to evaluate health policy impacts and to enhance risk communication with the public through mathematical modeling.