Halogenated aromatic pollutants in routine animal-derived food of south China: Occurrence, sources, and dietary intake risks.

Halogenated aromatic pollutants (HAPs) including polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated dibenzo-p-dioxins/furans (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) exhibit diverse toxicities and bio-accumulation in animals, thereby imposing risks on human via animal-derived food (ADF) consumption. Here we examined these HAPs in routine ADFs from South China and observed that PBDEs and PCBs showed statistically higher concentrations than PCDD/Fs and PBDD/Fs. PCDD/Fs and PCBs in these ADFs were mainly from the polluted feed and habitat of animals, except PCDD/Fs in egg, which additionally underwent selective biotransformation/progeny transfer after the maternal intake of PCDD/F-polluted stuff. PBDEs and PBDD/Fs were mostly derived from the extensive use of deca-BDE and their polluted environments. Significant interspecific differences were mainly observed for DL-PCBs and partly for PBDD/Fs and PBDEs, which might be caused by their distinct transferability/biodegradability in animals and the different living habit and habitat of animals. The dietary intake doses (DIDs) of these HAPs via ADF consumption were all highest for toddlers, then teenagers and adults. Milk, egg, and fish contributed most to the DIDs and risks for toddlers and teenagers, which results of several cities exceeded the recommended thresholds and illustrated noteworthy risks. Pork, fish, and egg were the top three risk contributors for adults, which carcinogenic and non-carcinogenic risks were both acceptable. Notably, PBDD/Fs showed the lowest concentrations but highest contributions to the total risks of these HAPs, thereby meriting continuous attention.

Dose-effect of exercise intervention on heart rate variability of acclimatized young male lowlanders at 3,680 m.

This study investigated whether exercise could improve the reduced HRV in an environment of high altitude. A total of 97 young, healthy male lowlanders living at 3,680 m for >1 year were recruited. They were randomized into four groups, of which three performed-low-, moderate-, and high-intensity (LI, MI, HI) aerobic exercise for 4 weeks, respectively. The remaining was the control group (CG) receiving no intervention. For HI, compared to other groups, heart rate (p = 0.002) was significantly decreased, while standard deviation of RR intervals (p < 0.001), SD2 of Poincaré plot (p = 0.046) and the number of successive RR interval pairs that differ by > 50 ms divided by total number of RR (p = 0.032), were significantly increased after intervention. For MI, significantly increase of trigonometric interpolation in NN interval (p = 0.016) was observed after exercise. Further, a decrease in systolic blood pressure (SBP) after high-intensity exercise was found significantly associated with an increase in SD2 (r = - 0.428, p = 0.042). These results indicated that there was a dose effect of different intensities of aerobic exercise on the HRV of acclimatized lowlanders. Moderate and high-intensity aerobic exercise would change the status of the autonomic nervous system (ANS) and decrease the blood pressure of acclimatized lowlanders exposed to high altitude.

Mixed-ownership reform and factor misallocation: Evidence from China.

An enterprise's ownership structure is crucial for factor allocation efficiency. We used Chinese firm-level data to investigate whether changes in state-owned enterprise ownership structure contribute to resource misallocation, leading to high-quality economic development. We found a U-shaped relationship between non-state shareholding and state-owned enterprises' resource allocation efficiency. An optimal range exists for non-state shareholding. When the shareholding of non-state shareholders reaches 10%-20%, the efficiency of resource allocation is at its highest. Additional research has revealed that mixed shareholding has varying impacts on resource allocation, displaying substantial heterogeneity. These insights offer valuable guidance for future mixed-ownership reforms and serve as a practical reference for economic reforms in other nations, particularly developing countries.

Replantation of digit-tip amputation caused by crush injuries with supermicrosurgery technique.

PURPOSE: Digit-tip amputation caused by crush injury is a common emergency scenario, and the management is full of challenges. The objective of this study was to demonstrate the application of the supermicrosurgery technique in replantation procedures for complex digit-tip amputations resulting from crush injuries, while also assessing functional and aesthetic outcomes. METHODS: We conducted a retrospective analysis of the data from 12 patients who underwent replantation of 15 digits in our department between July 2022 and June 2023. The outcomes of replantation, functional recovery (including return to work, cold tolerance, bone union, DASH score, VAS score, and two-point discrimination test), aesthetic results (including digit appearance, nail deformity, and pulp atrophy), and patient satisfaction were assessed. RESULTS: The amputation of 7 digits occurred within Tamai zone I level, 8 digits within Tamai zone II level, while 4 digits occurred within Ishikawa zone I level, 3 digits within Ishikawa zone II level, 7 digits within Ishikawa zone III level, and 1 digit within Ishikawa zone IV level. The replanted digits all survived (100%) without any indications of arterial insufficiency or venous congestion. The follow-up procedures were conducted on all 12 patients, with an average duration of 9.6 months (range, 6 to 18 months). The fracture successfully underwent healing at 9.2 weeks (range, 8 to 13 weeks). The mean VAS score was 1.75 points (range 0 to 4 points), the mean two-point discrimination test result was 5.72 mm (range 4.0 to 7.0 mm), and the mean DASH score was 9.78 points (range 3.33 to 22.5 points). All patients demonstrated cold tolerance and successfully resumed their pre-injury occupational activities. The nail deformity was observed in one digit following replantation within Tamai zone I, and in three digits following replantation within Tamai zone II; moreover, eight digits exhibited varying degrees of pulp atrophy. All patients expressed satisfaction with both functional and aesthetic outcomes. CONCLUSION: The successful replantation of digit-tip amputation caused by crush injury can be achieved through the application of supermicrosurgery technique, resulting in improved functional and aesthetic outcomes. Digit-tip replantation is a favorable and meaningful procedure with high patient satisfaction.

Sand Painting Generation Based on Convolutional Neural Networks.

Neural style transfer is an algorithm that transfers the style of one image to another image and converts the style of the second image while preserving its content. In this paper, we propose a style transfer approach for sand painting generation based on convolutional neural networks. The proposed approach aims to improve sand painting generation via neural style transfer, which can address the problem of blurred objects. Furthermore, it can reduce background noise caused by neural style transfers. First, we segment the main objects from the content image. Subsequently, we perform close-open filtering operations on the content image to obtain smooth images. Subsequently, we perform Sobel edge detection to process the images and obtain edge maps. Based on these edge maps and the input style image, we perform neural style transfer to generate sand painting images. Finally, we integrate the generated images to obtain the final stylized sand painting image. The results show that the proposed approach yields good visual effects from sand paintings. Moreover, the proposed approach achieves better visual effects for sand painting than the previous method.

Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19.

BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

Mixing state and influence factors controlling diurnal variation of particulate nitrophenol compounds at a suburban area in northern China.

Nitrophenols have received extensive attention due to their strong light-absorbing ability in the near-ultraviolet-visible region, which could be influenced by the atmospheric processes of nitrophenols. However, our knowledge and understanding of the formation and evolution of nitrophenols are still in the nascent stages. In the present study, the mixing states of four mononitrophenol particles (i.e., nitrophenol, methynitrophenol, nitrocatechol, and methoxynitrophenol), and one nitropolycyclic aromatic hydrocarbon particles (i.e., nitronaphthol (NN)) were investigated using a single-particle aerosol mass spectrometer (SPAMS) in November 2019 in Qingdao, China. The results showed, for the first time, that mononitrophenols and NN exhibit different mixing states and diurnal variations. Four mononitrophenols were internally mixed well with each other, and with organic acids, nitrates, potassium, and naphthalene. The diurnal variation in the number fraction of mononitrophenols presented two peaks at 07:00 to 09:00 and 18:00 to 20:00, and a valley at noon. Atmospheric environmental conditions, including NO2, O3, relative humidity, and temperature, can significantly influence the diurnal variation of mononitrophenols. Multiple linear regression and random forest regression models revealed that the main factors controlling the diurnal variation of mononitrophenols were photochemical reactions during the day and aqueous-phase reactions during the night. Unlike mononitrophenols, about 62-83% of NN were internally mixed with [NH4]+ and [H(NO3)2]-, but not with organic acids and potassium. The diurnal variation of NN was also different from that of mononitrophenols, generally increased from 17:00 to 10:00 and then rapidly decreaed from 11:00 to 16:00. These results imply that NN may have sources and atmospheric processes that are different from mononitrophenols. We speculate that this is mostly controlled by photochemical reactions and mixing with [NH4]+, which may influence the diurnal variation of NN in the ambient particles; however, this requires further confirmation. These findings extend our current understanding of the atmospheric formation and evolution of nitrophenols.

Aerobic Microbial Transformation of Fluorinated Liquid Crystal Monomer: New Pathways and Mechanism.

Fluorinated liquid crystal monomers (FLCMs) have been suggested as emerging contaminants, raising global concern due to their frequent occurrence, potential toxic effects, and endurance capacity in the environment. However, the environmental fate of the FLCMs remains unknown. To fill this knowledge gap, we investigated the aerobic microbial transformation mechanisms of an important FLCM, 4-[difluoro(3,4,5-trifluorophenoxy)methyl]-3, 5-difluoro-4'-propylbiphenyl (DTMDPB), using an enrichment culture termed as BG1. Our findings revealed that 67.5 ± 2.1% of the initially added DTMDPB was transformed in 10 days under optimal conditions. A total of 14 microbial transformation products obtained due to a series of reactions (e.g., reductive defluorination, ether bond cleavage, demethylation, oxidative hydroxylation and aromatic ring opening, sulfonation, glucuronidation, O-methylation, and thiolation) were identified. Consortium BG1 harbored essential genes that could transform DTMDPB, such as dehalogenation-related genes [e.g., glutathione S-transferase gene (GST), 2-haloacid dehalogenase gene (2-HAD), nrdB, nuoC, and nuoD]; hydroxylating-related genes hcaC, ubiH, and COQ7; aromatic ring opening-related genes ligB and catE; and methyltransferase genes ubiE and ubiG. Two DTMDPB-degrading strains were isolated, which are affiliated with the genus Sphingopyxis and Agromyces. This study provides a novel insight into the microbial transformation of FLCMs. The findings of this study have important implications for the development of bioremediation strategies aimed at addressing sites contaminated with FLCMs.

Glucagon-Like Peptide-1 Receptor Agonist and Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) exhibit glucose-lowering, weight-reducing, and blood pressure-lowering effects. Nevertheless, a debate exists concerning the association between GLP-1RA treatment and the risk of diabetic retinopathy (DR) in patients diagnosed with type 2 diabetes mellitus (T2DM). OBJECTIVE: To ascertain the risk of DR in patients with T2DM undergoing GLP-1RA treatment, we conducted a meta-analysis utilizing data derived from randomized placebo-controlled studies (RCTs). METHODS: A comprehensive literature search was conducted using PubMed, Cochrane Library, Web of Science, and EMBASE. We focused on RCTs involving the use of GLP-1RAs in patients with T2DM. Utilizing R software, we compared the risk of DR among T2DM patients undergoing GLP-1RA treatment. The Cochrane risk of bias method was employed to assess the research quality. RESULTS: The meta-analysis incorporated data from 20 RCTs, encompassing a total of 24,832 T2DM patients. Across all included trials, randomization to GLP-1 RA treatment did not demonstrate an increased risk of DR (odds ratio = 1.17; 95% CI 0.98-1.39). Furthermore, no significant heterogeneity or publication bias was detected in the analysis. CONCLUSION: The results of this systematic review and meta-analysis indicate that the administration of GLP-1 RA is not associated with an increased risk of DR. PROSPERO REGISTRATION IDENTIFIER: CRD42023413199.

New dechlorination products and mechanisms of tris(2-chloroethyl) phosphate by an anaerobic enrichment culture from a vehicle dismantling site.

End-of-life vehicles (ELVs) dismantling sites are the notorious hotspots of chlorinated organophosphate esters (Cl-OPEs). However, the microbial-mediated dechlorination of Cl-OPEs at such sites has not yet been explored. Herein, the dechlorination products, pathways and mechanisms of tris(2-chloroethyl) phosphate (TCEP, a representative Cl-OPE) by an anaerobic enrichment culture (ZNE) from an ELVs dismantling plant were investigated. Our results showed that dechlorination of TCEP can be triggered by reductive transformation to form bis(2-chloroethyl) phosphate (BCEP), mono-chloroethyl phosphate (MCEP) and by hydrolytic dechlorination to form bis(2-chloroethyl) 2-hydroxyethyl phosphate (TCEP-OH), 2-chloroethyl bis(2-hydroxyethyl) phosphate (TCEP-2OH), 2-chloroethyl (2-hydroxyethyl) hydrogen phosphate (BCEP-OH). The combination of 16S rRNA gene amplicon sequencing, quantitative real-time PCR (qPCR) and metagenomics revealed that the Dehalococcoides played an important role in the reductive transformation of TCEP to BCEP and MCEP. A high-quality metagenome-assembled genome (completeness >99% and contamination <1%) of Dehalococcoides was obtained. The sulfate-reducing bacteria harboring haloacid dehalogenase genes (had) may be responsible for the hydrolytic dechlorination of TCEP. These findings provide insights into microbial-mediated anaerobic transformation products and mechanisms of TCEP at ELVs dismantling sites, having implications for the environmental fate and risk assessment of Cl-OPEs at those sites.

Identifying luteolin as a potential drug for treating lung adenocarcinoma with COVID-19 affection based on integration analysis of pharmacology and transcriptome.

BACKGROUND: Lung adenocarcinoma (LUAD) is a major type of lung cancer worldwide, and under the pandemic coronavirus disease 2019 (COVID-19), its cancer burden is enlarged. This study aimed to explore potential drug targets and potential drugs for developing effective treatments for patients with both lung cancer and COVID-19. METHOD: The interaction network of molecule compounds-target genes was constructed based on Traditional Chinese Medicines (TCMs) and gene expression data from public databases. The potential effectiveness of drugs was analyzed by molecular docking and molecular dynamics simulation. Western blot, transfection assay, Immunohistochemistry (IHC) staining, and flow cytometry were performed to investigate the function of HSP90AA1 in LUAD cells. RESULT: Eight target genes (GSK3B, HMOX1, HSP90AA1, ICAM1, MAPK1, PLAU, RELA and TNFSF15.) were identified, and two of them (HSP90AA1 and RELA) were significantly associated with LUAD prognosis. Luteolin was discovered to bind with HSP90AA1. Moreover, In vitro cell experiments demonstrated that HSP90AA1 had higher expression in A549 cells, promoted cell viability and suppressed apoptosis in A549 cells and H1299 cells. CONCLUSION: HSP90AA1 was a target gene for further designing effective drugs for LUAD patients. Luteolin was a potential drug for treating patients with both LUAD and COVID-19.

Occurrence and carcinogenic potential of airborne PBDD/Fs and PCDD/Fs around a large-scale municipal solid waste incinerator: A long-term passive air sampling study.

Municipal solid waste incinerator (MSWI) not only is deemed one of the uppermost sources of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), but also produces substantial amount of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) owing to the existence of brominated flame retardants (BFRs) in the waste. So far, however, PBDD/Fs in the vicinal environments of MSWI and their associated risks remain rarely studied. Based on a one-year passive air sampling (PAS) scheme, we investigated airborne PBDD/Fs and PCDD/Fs around a large-scale MSWI that has been operated for multi-years. Both the concentrations of PBDD/Fs and PCDD/Fs showed spatially decreasing trends with the distance away from the MSWI, confirming the influence of the MSWI on the dioxin levels in its ambient air. But its influence on PBDD/Fs was less because PBDD/Fs exhibit lower volatility and therefore lower gaseous concentrations than PCDD/Fs. Compared to the existing global data of airborne PCDD/Fs and PBDD/Fs, our data of the MSWI vicinity were at medium levels, despite PAS samples only represent the concentrations of gaseous dioxins in theory. The seasonal data suggest that meteorological conditions exerted apparent influences over the concentrations and sources of airborne dioxins around the MSWI. As for PCDD/Fs, the MSWI was diagnosed as their uppermost source, followed by local traffic and volatilization/deposition. Whereas the top three PBDD/F sources were related to PBDEs, bromophenol/bromobenzene, and traffic vehicles, respectively. The bioassay-derived TEQs based on the aryl hydrocarbon receptor activation of airborne dioxins around the MSWI were one or two orders of magnitudes higher than their concentration-based TEQs, and the corresponding carcinogenic risks at some MSWI-vicinal sites exceeded the acceptable threshold proposed by the U. S. EPA (10-6 âˆ¼ 10-4) and deserve continuous attention.

Long Noncoding RNA ACTA2-AS1 Inhibits Cell Growth and Facilitates Apoptosis in Gastric Cancer by Binding with miR-6720-5p to Regulate ESRRB.

Gastric cancer (GC) is a common malignant tumor, posing a great threat to human's health and life. Previous studies have suggested aberrant expression of long non-coding RNAs (lncRNAs) in GC. This study elucidated the effects of lncRNA ACTA2-AS1 on the biological characteristics of GC. Gene expression in stomach adenocarcinoma (STAD) samples compared with normal tissues and the correlation between gene expression and prognosis of STAD patients were analyzed using bioinformatic tools. Gene expression at protein and mRNA levels in GC and normal cells was tested by western blotting and RT-qPCR. The subcellular localization of ACTA2-AS1 in AGS and HGC27 cells was identified by nuclear-cytoplasmic fractionation and FISH assay. EdU, CCK-8, flow cytometry analysis, TUNEL staining assays were conducted to evaluate the role of ACTA2-AS1 and ESRRB on GC cellular behaviors. The binding relationship among ACTA2-AS1, miR-6720-5p and ESRRB was verified by RNA pulldown, luciferase reporter assay and RIP assay. LncRNA ACTA2-AS1 was underexpressed in GC tissues and cell lines. ACTA2-AS1 elevation suppressed GC cell proliferation and induced apoptosis. Mechanistically, ACTA2-AS1 directly bound to miR-6720-5p and subsequently promoted the expression of target gene ESRRB in GC cells. Furthermore, ESRRB knockdown reversed the influence of ACTA2-AS1 overexpression on GC proliferation and apoptosis. ACTA2-AS1 plays an antioncogenic role in GC via binding with miR-6720-5p to regulate ESRRB expression.

EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have a significant therapeutic effect in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. However, the acquired resistance greatly limits the survival benefit of EGFR-TKIs for EGFR-mutant NSCLC patients. We aimed to assess the efficacy and safety of stereotactic body radiotherapy (SBRT) plus EGFR-TKIs in these patients. METHODS: In this prospective, randomized, controlled, phase 2 study, participants were recruited from 4 different hospitals in Wuhan, China. Eligible patients were histologically confirmed to have NSCLC with an EGFR-sensitive mutation (19DEL or 21L858R) and diagnosed at stage IV. Patients who had received first-line EGFR-TKIs treatment including gefitinib, erlotinib, and icotinib and achieved stable disease or partial response were enrolled after three months. Eligible participants were randomly assigned (1:1) to receive SBRT plus EGFR-TKIs or EGFR-TKIs treatment alone. In the combination-group, different tumor sites were irradiated at doses ranging from 30-50 Gy in five fractions. Considering the short duration of SBRT, the TKIs were continued during the radiotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and safety. This study was registered at ClinicalTrials.gov, with the registration number of NCT03595644. RESULTS: Between May 4, 2018 and Dec 20, 2019, 74 patients were screened, of whom 62 patients were enrolled and randomized. The study was closed early with 62/72 patients due to slow accrual. The enrolled patients were randomly assigned to receive SBRT plus EGFR-TKI(n = 31) or EGFR-TKI alone (n = 31). One patient who was randomized to the SBRT plus EGFR-TKI group refused to receive SBRT during the treatment, and, 61 patients were included the modified intention-to-treat (mITT) analysis, with 30 in the SBRT plus EGFR-TKI and 31 in the EGFR-TKI group. As of the clinical cutoff date (Feb 14, 2022), the median follow-up was 29.4 months (IQR 6.9-38.9). The median PFS of the EGFR-TKI group and SBRT combination group was 9.0 vs 17.6 months (hazard ratio [HR] = 0.52, 95% confidence interval [95%CI], 0.31-0.89, P = 0.016). Meanwhile, the median OS was 23.2 vs 33.6 months (HR [95%CI], 0.53(0.30-0.95); P = 0.026). There was no grade 3 or greater toxicity observed in either group, the grade 2 adverse events were 50% in the EGFR-TKIs + SBRT group while the percentage was 45.2% in the EGFR-TKIs group. CONCLUSIONS: The addition of SBRT significantly delayed the onset of acquired resistance to EGFR-TKIs and prolonged the PFS and OS of patients. Radiotherapy of the primary lesion alone might be superior to metastatic sites. Further confirmatory studies are needed to confirm our findings.

Single-atomic platinum on fullerene C60 surfaces for accelerated alkaline hydrogen evolution.

The electrocatalytic hydrogen evolution reaction (HER) is one of the most studied and promising processes for hydrogen fuel generation. Single-atom catalysts have been shown to exhibit ultra-high HER catalytic activity, but the harsh preparation conditions and the low single-atom loading hinder their practical applications. Furthermore, promoting hydrogen evolution reaction kinetics, especially in alkaline electrolytes, remains as an important challenge. Herein, Pt/C60 catalysts with high-loading, high-dispersion single-atomic platinum anchored on C60 are achieved through a room-temperature synthetic strategy. Pt/C60-2 exhibits high HER catalytic performance with a low overpotential (η10) of 25 mV at 10 mA cm-2. Density functional theory calculations reveal that the Pt-C60 polymeric structures in Pt/C60-2 favors water adsorption, and the shell-like charge redistribution around the Pt-bonding region induced by the curved surfaces of two adjacent C60 facilitates the desorption of hydrogen, thus favoring fast reaction kinetics for hydrogen evolution.

Terahertz spectra of proteinuria and non-proteinuria.

In clinical practice, proteinuria detection is of great significance in the diagnosis of kidney diseases. Dipstick analysis is used in most outpatient settings to semi-quantitatively measure the urine protein concentration. However, this method has limitations for protein detection, and alkaline urine or hematuria will cause false positive results. Recently, terahertz time-domain spectroscopy (THz-TDS) with strong hydrogen bonding sensitivity has been proven to be able to distinguish different types of biological solutions, which means that protein molecules in urine may have different THz spectral characteristics. In this study, we performed a preliminary clinical study investigating the terahertz spectra of 20 fresh urine samples (non-proteinuria and proteinuria). The results showed that the concentration of urine protein was positively correlated with the absorption of THz spectra at 0.5-1.2 THz. At 1.0 THz, the pH values (6, 7, 8, and 9) had no significant effect on the THz absorption spectra of urine proteins. The terahertz absorption of proteins with a high molecular weight (albumin) was greater than that of proteins with a low molecular weight (ß2-microglobulin) at the same concentration. Overall, THz-TDS spectroscopy for the qualitative detection of proteinuria is not affected by pH and has the potential to discriminate between albumin and ß2-microglobulin in urine.

HbA1c is a predictive factor of severe coronary stenosis and major adverse cardiovascular events in patients with both type 2 diabetes and coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is not only a macrovascular complication of type 2 diabetes mellitus (T2DM). Cardiovascular disease (CVD) is one of the leading causes of mortality among individuals with T2DM. Reducing the risk of adverse cardiovascular events (MACE) is crucial for the management of patients with CHD. This study aimed to investigate the effect of glycemic control on CHD severity and 3-point MACE (3p-MACE) risk in patients with T2DM and CHD. METHODS: 681 patients with both T2DM and CHD throughout October 2017 and October 2021 who were hospitalized in the second affiliated hospital of Nanchang university were included. A total of 300 patients were eventually enrolled in this retrospective cohort research. The severity of CHD in these patients was assessed, and the primary outcome during follow-up was recorded, with the primary result being the 3-point major adverse cardiovascular event (3p-MACE). The correlation between baseline glycated hemoglobin A1c (b-HbA1c) and the severity of CHD was evaluated by logistic regression analysis. The effect of b-HbA1c and follow-up HbA1c (f-HbA1c) levels on the risk of 3p-MACE were investigated by cox regression analysis. RESULTS: b-HbA1c was positively correlated with the severity of CHD (r = 0.207, p = 0.001), and patients with b-HbA1c > 9% were more likely to have severe CHD. The HRs for b-HbA1c and f-HbA1c on the risk of 3p-MACE were 1.24 (95% CI 0.94-1.64, p = 0.123) and 1.32 (95% CI 1.02-1.72, p = 0.036), respectively. Patients with f-HbA1c ≥8.6% had a higher risk of 3p-MACE than f-HbA1c < 8.6% (HR = 1.79, 95% CI 1.16-2.79, p = 0.009). CONCLUSION: In patients with both T2DM and CHD, b-HbA1c was an independent predictive factor of severe CHD. f-HbA1c was an independent predictive factor of 3p-MACE. Having the f-HbA1c below 8.6% significantly reduced the risk of 3p-MACE.

Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.

Effects of Solvents on Reaction Products: Synthesis of Endohedral Metallofullerene Oxazoline and Epoxide.

Herein, we performed the reactions of M3N@Ih-C80 (M = Sc and Lu) with the methanol (CH3OH) solution of TBAOH (note that both CH3O- and OH- are nucleophiles) in benzonitrile (PhCN) and dimethylformamide, respectively. It is found that OH- ions rather than CH3O- ions selectively attacked the fullerene cage to form the M3N@C80--O- intermediate. Although the fullerene cage is initially attacked by OH- in both PhCN and DMF solvents, the products are quite different. In PhCN, two isomeric Sc3N@Ih-C80 fullerooxazoline heterocyclic products (1 and 2) were synthesized. Whereas, in DMF, an epoxide of Lu3N@Ih-C80 (3) was obtained. The preference for fullerooxazoline formation over that of fullerene epoxy in PhCN is well explained by density functional theory calculations. Plausible reaction mechanisms for the formation of metallofullerene oxazoline and epoxide were proposed based on the experimental and theoretical results.

Ginsenoside Rg3 Sensitizes Nasopharyngeal Carcinoma Cells to Radiation by Suppressing Epithelial Mesenchymal Transition.

Radioresistance restrains the therapeutic effect of nasopharyngeal carcinoma (NPC). Ginsenoside Rg3 (Rg3), an active pharmaceutical component extracted from ginseng, shows antitumor effects in various cancers. In this study, we aimed to determine whether Rg3 sensitized NPC cells to radiation and to explore the possible mechanisms. Our results revealed that Rg3 increased radiosensitivity in both HNE1 and CNE2 cell lines. Radiation induced epithelial mesenchymal transition (EMT) in NPC cells and Rg3 blocked this effect. In addition, Rg3 attenuated radiation-induced epidermal growth factor receptor (EGFR) nuclear transport and DNA-dependent protein kinase expression. What's more, Rg3 significantly accelerated the apoptosis rates in irradiated NPC cells. In summary, our data suggested that Rg3 sensitized NPC cells to radiation and suppressed radiation-induced EMT. This effect is mediated through restrained EGFR nuclear translocation and increased cell apoptosis. Thus, Rg3 may be a potential radiation sensitizing agent for NPC.