Synergistic oxidation of humic acid treated by H2O2/O3 activated by CuCo/C with high efficiency and wide pH range.

Combination of oxidation processes are one of the most promising humic acid treatment technologies. Single oxidant or even two oxidants in advance oxidation process can hardly achieve satisfactory removal efficiency of refractory organic matter, mainly humic acid, in the treatment process of reverse osmosis concentrates from landfill leachate. To solve this problem, this study investigated the synergistic degradation of Humic acid (HA) using a Cu and Co supported on carbon catalyst (CuCo/C) in a Hydrogen peroxide (H2O2) with ozone (O3) system. The catalyst was characterized by performing SEM, XRD, BET, XPS and FTIR technologies. UV-vis spectra, 3D Excitation Emission Matrix Spectra (3D-EEM) and gas chromatography-mass spectrometry (GC-MS) were applied for exploring degradation mechanism of HA. To further understand the oxidation mechanism, electron paramagnetic resonance (EPR) was used to evaluate the generation of hydroxyl (·OH) and superoxide radicals (O2·-). As a result, CuCo/C catalyst possessed stable catalytic performance for HA degradation with a wide pH range from 5 to 8, while T = 40 °C，catalyst dosage of 2.4 g/L，O3 intake rate of 0.15 g/min and H2O2 dosage of 1.92 mL/L, the degradation rate of total organic carbon (TOC) achieved 40-46.5 mg·L-1min-1. As affirmed by the EPR, ·OH and O2·- were effectively generated with addition of the CuCo/C catalyst. Degradation performance of UV254 proved that the catalytic activity can still be maintained above 95% with removal rate of 82% after 5 cycles reuse. GC-MS shows that the oxidation products mainly consist of amide, benzoheterocyclic ring and carboxylic acid. This work promotes an effective method for degrading HA, which has the potential for satisfactory application in landfill leachate.

Molecular imaging of fibroblast activity in pressure overload heart failure using [68 Ga]Ga-FAPI-04 PET/CT.

PURPOSE: We aimed to evaluate whether [68 Ga]Ga-FAPI-04 PET/CT could characterize the early stages of cardiac fibrosis in pressure overload heart failure. METHODS: Sprague-Dawley rats underwent abdominal aortic constriction (AAC) (n = 12) and sham surgery (n = 10). All rats were scanned with [68 Ga]Ga-FAPI-04 PET/CT at 2, 4, and 8 weeks after surgery. The expression of fibroblast activation protein (FAP) in the myocardium was detected by immunohistochemistry. [68 Ga]Ga-FAPI-04 PET signal and FAP expression were compared between two groups. RESULTS: Compared with the sham group, the AAC group presented with decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in diastole (LVIDd) and systole (LVIDs) at 4 and 8 weeks (all p < 0.01). The AAC group showed higher [68 Ga]Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8 weeks, and FAPI increased significantly from 2 to 8 weeks (all p < 0.001). Immunohistochemistry confirmed the higher density of the FAP+ area in the AAC group. The intensity of the [68 Ga]Ga-FAPI-04 correlated with the density of the FAP+ area (p < 0.001). The expression of the [68 Ga]Ga-FAPI-04 at 4 weeks correlated with the deterioration of cardiac function at 8 weeks (EF: R = - 0.87; FS: R = - 0.72; LVIDd: R = 0.77; LVIDs: R = 0.79; all p < 0.001). The AAC group also showed an increased [68 Ga]Ga-FAPI-04 signal in the liver, peaking at 4 weeks and then declining. Cardiac and liver PET signals correlated at 4 weeks in the AAC group (R = 0.69, p = 0.0010), suggesting an early fibrotic link between organs. A combination of the [68 Ga]Ga-FAPI-04 intensity in the heart and liver at 4 weeks better predicted the deterioration of cardiac function at 8 weeks. CONCLUSIONS: The activated fibroblasts in the heart and liver after pressure overload can be monitored by [68 Ga]Ga-FAPI-04 PET/CT, which reveals an early fibrotic link in cardio-liver interactions and could better predict nonischemic heart failure prognosis.

Association between prenatal PM2.5 exposure and the risk of large for gestational age.

BACKGROUND: The relationship between particulate matter <2.5 µm (PM2.5) and large for gestational age (LGA) is unclear, and studies conducted in highly polluted areas are lacking. We aimed to explore the association between PM2.5 and the risk of LGA in China. METHODS: Maternal and neonatal characteristics were collected in the National Prepregnancy Examination Project. The definition of LGA was neonates with a weight over the 90th percentile for gestational age. Logistic regression was used to evaluate the relationship between PM2.5 exposure and the risk of LGA. The dose-response relationship was evaluated using a restricted cubic spline model. RESULTS: There were 196,243 mother-neonate pairs included, among which the percentage of LGA was 15.3%. The average PM2.5 concentration was 75.29 µg/m3. A 10 µg/m3 increase in PM2.5 during the whole pregnancy was associated with an increased risk of LGA (odds ratio (OR) 1.097, 95% confidence interval (CI) 1.091-1.103). Pregnant women in the high-exposure group had a higher risk of giving birth to an LGA infant (OR 1.37, 95% CI 1.33-1.41). There was a nonlinear relationship between PM2.5 concentration and the risk of LGA, and the risk increased more rapidly at higher PM2.5 levels. CONCLUSIONS: Prenatal exposure to PM2.5 was linked to an increased risk of LGA. IMPACT: A nation-wide study in a highly polluted country suggested the association between prenatal PM2.5 exposure and LGA. A trimester-specific relationship between PM2.5 exposure and LGA was established. Call for attention on the pregnant women in highly polluted areas who were in high risk of giving birth to LGA.

Super Early Scan of PSMA PET/CT in Evaluating Primary and Metastatic Lesions of Prostate Cancer.

68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT has been widely used in the diagnosis of prostate cancer (PCa); however, the urine lead shielding resulting from the urinary metabolism of tracers may obstruct the detection of surrounding metastasis. In this research, the additive value of super early scanning in diagnosing primary lesions and metastasis in the pelvic cavity was evaluated. Firstly, the differentiation efficiency of 68Ga-PSMA-11 PET scanned at 3 min post-injection (min P.I.) was measured in PSMA-positive (22rv1 cells) and PSMA-negative (PC3 cells) model mice. Secondly, 106 patients were scanned at 3 min P.I. for the pelvic cavity and then scanned as a standard protocol at 45 min P.I. In the results, the differential diagnosis of PSMA expression was completely reflected as early as 3 min P.I. for mice models. For patients, when correlated with the Gleason score, the quantitative results of the super early scan displayed a comparable correlation coefficient with the routine scan. The target to bladder ratios increased from 1.44 ± 2.40 at 45 min to 10.10 ± 19.10 at 3 min (p < 0.001) for the primary lesions, and it increased from 0.99 ± 1.88 to 9.27 ± 23.03 for metastasis. Meanwhile, the target to background ratios increased from 2.21 ± 2.44 at 3 min to 19.13 ± 23.93 at 45 min (p < 0.001) for the primary lesions, and it increased from 1.68 ± 2.71 to 12.04 ± 18.73 (p < 0.001) for metastasis. In conclusion, super early scanning of 68Ga-PSMA-11 PET/CT added referable information for metastasis detection in order to avoid disturbing tracer activity in the urinary system.

PR10/Bet v1-like Proteins as Novel Contributors to Plant Biochemical Diversity.

Pathogenesis-related (PR) proteins constitute a broad class of plant proteins with analogues found throughout nature from bacteria to higher eukaryotes. PR proteins were first noted in plants as part of the hypersensitive response, but have since been assigned an array of biological roles. The PR10/Bet v1-like proteins are a subset of PR proteins characterized by an ability to bind a wide range of lipophilic ligands, uniquely positioning them as contributors to specialized biosynthetic pathways. PR10/Bet v1-like proteins participate in the production of plant alkaloids and phenolics including flavonoids, both as general binding proteins and in special cases as catalysts. Owing initially to the perceived allergenic properties of PR10/Bet v1-like proteins, many were studied at the structural level to elucidate the basis for ligand binding. These studies provided a foundation for more recent efforts to understand higher-level structural order and how PR10/Bet v1-like proteins catalyse key reactions in plant pathways. Synthetic biology aimed at reconstituting plant-specialized metabolism in microorganisms uses knowledge of these proteins to fine-tune performance in new systems.

Relationship between the duration of smoking and blood pressure in Han and ethnic minority populations: a cross-sectional study in China.

BACKGROUND: Evidence for correlation between the cigarette use and blood pressure change remains ambiguous. This study modelled relationship between the duration of smoking and systolic blood pressure in a large national multi-ethnic cross-sectional survey in China. METHODS: Participants were selected through a multi-stage probability sampling procedure from 2012 to 2017. Former or current smokers were included in this study, whose smoking behaviour, blood pressure, and other demographic information were collected and measured through a face-to-face interview. Linear and non-linear relationships between the duration of smoking and systolic blood pressure were analysed and differences of the association between Han and minority populations were specially checked. RESULTS: A total of 8801 participants were enrolled in this study. Prevalence of hypertension was 41.3 and 77.8% were current smokers. For every additional year of smoking duration, systolic blood pressure raised by 0.325 mmHg (95% CI 0.296 to 0.354 mmHg, P <  0.001). The Chinese minority populations may suffer more from the elevated blood pressure in long-term smoking than Han populations (0.283 mmHg (95% CI 0.252 to 0.314 mmHg, P <  0.001) versus 0.450 mmHg (95% CI 0.380 to 0.520 mmHg, P <  0.001) raise in systolic blood pressure with each additional year of smoking in minority and Han populations). CONCLUSIONS: Smoking is associated with raised systolic blood pressure in Chinese population. This association is notedly stronger in Chinese minority populations.

Outcomes of Transsphenoidal Surgery in Cushing Disease Patients with Negative Pituitary Magnetic Resonance Imaging Findings: A Single-Center Experience.

OBJECTIVE: Transsphenoidal surgery (TSS) is a first-line treatment for Cushing disease (CD). However, a subset of patients with CD have no visible adenoma on magnetic resonance imaging (MRI), and whether MRI results affect surgical outcomes is controversial. The aim of this study was to compare the surgical outcomes of CD patients with negative MRI findings to those of patients with positive MRI findings. METHODS: The clinical features and outcomes of CD patients who underwent TSS between January 2000 and July 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinologic, histopathologic, surgical outcomes, and a minimum 12-month follow-up of 125 consecutive CD patients with negative MRI findings were compared with those of 1,031 consecutive CD patients with MRI-visible adenomas. RESULTS: The total remission rate was 73.3% after TSS, and 11.8% of patients experienced recurrence. Of 1,031 patients with MRI-visible adenomas, postoperative remission was achieved in 762 patients (73.9%), and the recurrence of CD was observed in 94 (12.3%) patients. Of the 125 patients with negative MRI findings, postoperative remission was achieved in 85 (68%) patients, and recurrence was observed in 6 (7.1%) patients. The remission rate and recurrence rate were not significantly different between patients with negative MRI findings and those with positive MRI findings (all P>.05). The remission rate was not significantly different between patients who did or did not undergo bilateral inferior petrosal sinus sampling (BIPSS) in patients with negative MRI findings (P>.05). In the patients with negative MRI findings who underwent BIPSS, the remission rate of patients with positive BIPSS results was not different from that in patients with negative BIPSS results (P>.05). The lack of prior TSS, the detection of a tumor during operation, and pathologic confirmation of adenoma were associated with a higher surgical remission rate in patients with negative MRI findings (all P<.05). Similar results were observed in the patients with positive MRI findings (all P<.05). In addition, the major perioperative complications, including intraoperative cerebrospinal fluid leakage, hypopituitarism, and transient diabetes insipidus, were not related to the MRI results (all P>.05). CONCLUSION: The remission rate and recurrence rate were not different between patients with negative MRI findings and those with positive MRI findings. If CD is clearly diagnosed according to biochemical tests, radiologic examinations, and BIPSS, we recommend TSS as the first-line treatment for patients, even if the MRI results are negative.

Initial classification of pediatric hearing impairment using behavioral measures of early prelingual auditory development.

OBJECTIVE: Determine the sensitivity, specificity, and accuracy of pediatric hearing loss classification using behavioral evidence of early prelingual auditory development (EPLAD). Validate behavioral measures of EPLAD. DESIGN: EPLAD was assessed in a prospective sample of hearing-impaired children using the infant-toddler meaningful auditory integration scale (ITMAIS/MAIS). Hearing losses were classified using tone-burst auditory brainstem response (ABR) and ITMAIS/MAIS scores. This process was repeated in a second retrospective sample. STUDY SAMPLE: The prospective sample was comprised of 139 hearing-impaired children under five years of age. Approximately equal proportions of mild-moderate, severe, and profound losses were included. The second retrospective sample was comprised of case records for 144 hearing-impaired children meeting the same selection criteria. This sample contained more than 80% profound losses. RESULTS: EPLAD trajectories reached different asymptotes after two years of age, depending on the severity of hearing loss, allowing children over this age to be classified. The sensitivity of EPLAD classifications was over 90%; specificity was over 82%; and accuracy was over 88%. CONCLUSIONS: Behavioral evidence of EPLAD provides an initial means of classifying pediatric hearing losses which can facilitate initial treatment options prior to diagnostic evaluation with tone-burst ABR.

Iron-Catalyzed Denitrogenative Annulation Reactions between α-Azido Acetamides and Cyclic Ketones.

We report an FeCl2-catalyzed annulation reaction between α-azido acetamides and cyclic ketones. Two types of α,ß-unsaturated γ-lactam products can be obtained, depending on the reaction conditions. When α-azido acetamides were reacted with cyclohexanone, 8-amino-5,6,7,8-tetrahydro-1H-indol-2(4H)-ones were obtained when a primary amine was present in the reaction system; conducting the reaction in the presence of 2-aminobenzenesulfonic acid, on the contrary, resulted in the formation of 5,6-dihydro-1H-indol-2(4H)-ones. Cycloheptanone and cyclooctanone reacted in the same way as cyclohexanone. The reactions proceed via the intermediacy of 2-iminoacetamides, which are formed by FeCl2-facilitated dinitrogenation of α-azido acetamides. These reactions constitute a new strategy for expanding the synthetic dimensions of organic azides.

Antihyperlipidemic drug rosuvastatin suppressed tumor progression and potentiated chemosensitivity by downregulating CCNA2 in lung adenocarcinoma.

Rosuvastatin (RSV) is widely used to treat hyperlipidemia and hypercholesterolemia and is recommended for the primary and secondary prevention of cardiovascular diseases (CVD). In this study, we aimed to explore its action and mechanism in lung adenocarcinoma (LUAD) therapy. Lewis and CMT64 cell-based murine subcutaneous LUAD models were employed to explore the effects of RSV monotherapy combined with cisplatin and gemcitabine. Human lung fibroblasts and human LUAD cell lines were used to assess the effects of RSV on normal and LUAD cells. Bioinformatics and RNA interference were used to observe the contribution of cyclin A2 (CCNA2) knockdown to RSV inhibition and to improve chemosensitivity in LUAD. RSV significantly suppressed grafted tumor growth in a murine subcutaneous LUAD model and exhibited synergistic anti-tumor activity with cisplatin and gemcitabine. In vitro and in vivo experiments demonstrated that RSV impaired the proliferation and migration of cancer cells while showing little inhibition of normal lung cells. RNA interference and CCK8 detection preliminarily indicated that RSV inhibited tumor growth and enhanced the chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2. RSV suppressed LUAD progression and enhanced chemosensitivity to cisplatin and gemcitabine by downregulating CCNA2, which should be prior consideration for the treatment of LUAD, especially for patients co-diagnosed with hyperlipidemia and hypercholesterolemia.

Comparison of Aroma Compounds and Sensory Characteristics between Two Different Types of Rice-Based Baijiu.

Rice-based Baijiu has gained popularity in the Chinese market. Qingya-flavored Baijiu, a variant of Xiaoqu-fermented Baijiu, employs rice as its primary raw material, with an improved production process compared to traditional rice-flavored Baijiu. We comprehensively characterized and compared the aroma profiles of these two rice-based Baijiu types using static sensory experiments (QDA, quantitative descriptive analysis) and dynamic sensory experiments (TDS, temporal dominance of sensations). Qingya-flavored Baijiu exhibited pronounced plant, oily, and roasted aromas, while traditional rice-flavored Baijiu displayed more prominent fruity, floral, and sour notes. Utilizing GC-O-MS (gas chromatography-olfactometry-mass spectrometry) and multi-method quantification, we qualitatively and quantitatively analyzed 61 key aroma compounds, identifying 22 compounds with significant aroma contributions based on odor activity values (OAVs). Statistical analyses, combining sensory and chemical results, were conducted to predict important aroma compounds responsible for the aroma differences between the two Baijiu types. Aroma Recombination and Omission experiments showed that seven compounds play key roles in the aroma of Qingya-flavored Baijiu, including (2E,4E)-Deca-2,4-dienal, linalool, apricolin, ethyl acetate, ethyl isobutyrate, ethyl caprylate, and ethyl isovalerate.

A combination weighting method for debris flow risk assessment based on t-distribution and linear programming optimization algorithm.

Debris flow risk assessment can provide some reference for debris flow prevention and control projects. In risk assessment, researchers often only focus on the impact of objective or subjective indicators. For this purpose, this paper proposed a weight calculation method based on t-distribution and linear programming optimization algorithm (LPOA). Taking 72 mudslides in Beichuan County as an example, this paper used analytic hierarchy process (AHP), entropy weight method (EWM) and variation coefficient method (VCM) to obtain the initial weights. Based on the initial weights, weight intervals with different confidence levels were obtained by t-distribution. Subsequently, the final weights were obtained by LOPA in the 90% confidence interval. Finally, the final weights were used to calculate the risk score for each debris flow, thus delineating the level of risk for each debris flow. The results showed that this paper's method can avoid overemphasizing the importance of a particular indicator compared to EWM and VCM. In contrast, EWM and VCM ignored the effect of debris flow frequency on debris flow risk. The assessment results showed that the 72 debris flows in Beichuan County were mainly dominated by moderate and light risks. Of these, there were 8 high risk debris flows, 24 medium risk debris flows, and 40 light risk debris flows. The excellent triggering conditions provide favorable conditions for the formation of high-risk debris flows. Slightly and moderate risk debris flows are mainly located on both sides of highways and rivers, still posing a minor threat to Beichuan County. The proposed fusion weighting method effectively avoids the limitations of single weight calculating method. Through comparison and data analysis, the rationality of the proposed method is verified, which can provide some reference for combination weighting method and debris flow risk assessment.

CARDS, a Novel Prognostic Index for Risk Stratification and In-Hospital Monitoring.

Background: Sodium fluctuation is independently associated with clinical deterioration. We developed and validated a prognostic index based on sodium fluctuation for risk stratification and in-hospital monitoring. Methods: This study included 33,323 adult patients hospitalized at a tertiary care hospital in 2014. The first 28,279 hospitalizations were analyzed to develop the model and then the validity of the model was tested using data from 5044 subsequent hospitalizations. We predict in-hospital mortality using age, comorbidity, range of sodium fluctuation, and duration of sodium fluctuation, abbreviated as CARDS. Results: In-hospital mortality was similar in the derivation (0.6%) and validation (0.4%) cohorts. In the derivation cohort, four independent risk factors for mortality were identified using logistic regression: age (66-75, 2 points; >75, 3 points); Charlson comorbidity index (>2, 5 points); range of sodium fluctuation (7-10, 4 points; >10, 10 points); and duration of fluctuation (≤3, 3 points). The AUC was 0.907 (95% CI: 0.885-0.928) in the derivation cohort and 0.932 (95% CI: 0.895-0.970) in the validation cohort. In the derivation cohort, in-hospital mortality was 0.106% in the low-risk group (0-7 points), 1.076% in the intermediate-risk group (8-14 points), and 8.463% in the high-risk group (15-21 points). In the validation cohort, in-hospital mortality was 0.049% in the low-risk group, 1.064% in the intermediate-risk group, and 8.403% in the high-risk group. Conclusions: These results suggest that patients at low, intermediate, and high risk for in-hospital mortality may be identified by CARDS mainly based on sodium fluctuation.

Stability analysis of rainfall-induced landslide considering air resistance delay effect and lateral seepage.

Accumulation landslides are prone to occur during the continuous infiltration of heavy rainfall, which seriously threatens the lives and property safety of local residents. In this paper, based on the Green-Ampt (GA) infiltration model, a new slope rainfall infiltration function is derived by combining the effect of air resistance and lateral seepage of saturated zone. Considering that when the soil layer continues to infiltrate after the saturation zone is formed, the air involvement cannot be discharged in time, which delays the infiltration process. Therefore, the influence of air resistance factor in soil pores is added. According to the infiltration characteristics of finite long slope, the lateral seepage of saturated zone is introduced, which makes up for the deficiency that GA model is only applicable to infinite long slope. Finally, based on the seepage characteristics of the previous analysis, the overall shear strength criterion is used to evaluate the stability of the slope. The results show that the safety factor decreases slowly with the increase of size and is inversely correlated with the slope angle and initial moisture content. The time of infiltration at the same depth increases with the increase of size and slope angle, and is inversely correlated with the initial moisture content, but is less affected by rainfall intensity. By comparing with the results of experimental data and other methods, the results of the proposed method are more consistent with the experimental results than other methods.

Comparison of moving bed biofilm reactor and bio-contact oxidation reactor start-up with heterotrophic nitrification-aerobic denitrification bacteria and activated sludge inoculation under high ammonia nitrogen conditions.

To overcome poor ammonia tolerance and removal performance of bio-contact oxidation (BCO) reactor inoculated with activated sludge for high-ammonia nitrogen (NH4+-N) chemical wastewater treatment, this study compared inoculating heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria in moving bed biofilm reactor (MBBR) with activated sludge inoculation in BCO reactor under simulated high NH4+-N conditions. Results revealed that MBBR achieved faster biofilm formation (20 days vs. 100 days for BCO) with notable advantages: 27.6 % higher total nitrogen (TN) and 29.9 % higher NH4+-N removal efficiency than BCO. Microbial analysis indicated optimal enrichment of the key nitrogen removal (NR) bacterium Alcaligenes, leading to increased expression of NR enzymes hydroxylamine reductase, ensuring the superior NR efficiency of the MBBR. Additionally, functional enzymes and genes analysis speculated that the NR pathway in MBBR was: NH4+-N â†’ NH2OH â†’ NO3--N â†’ NO2--N â†’ NO â†’ N2O â†’ N2. This research offers a practical and theoretical foundation for extending HN-AD bacteria-inoculated MBBR processes.

[Change of serum myeloperoxidase and lipoxin A4 level in coronary heart disease patients with anxiety and/or depression].

OBJECTIVE: To investigate the change of serum myeloperoxidase (MPO) and lipoxin A4 (LXA4) in coronary heart disease (CHD) patients with anxiety and depression and its clinical significance. METHODS: From December 2010 to February 2011, 143 CHD patients and 44 non-CHD patients (the control group) hospitalized in the Department of Cardiology at the Second Xiangya Hospital were enrolled. The hospital anxiety and depression scale (HADS) was used to evaluate the psychological state of all patients and the CHD patients were assigned to an anxiety and depression group (n=57) or a non-depression and anxiety group (n=86). The serum levels of high sensitive C-reactive protein (Hs-CRP), MPO, and LXA4 were examined, and the ratio of MPO and LXA4 (M/L) was calculated. RESULTS: The levels of Hs-CRP, MPO, and LXA4 as well as M/L ratios in both CHD groups were significantly higher than those in the control group (all P<0.01). Compared with the non-anxiety and depression group, the levels of MPO and LXA4, and M/L ratios in the anxiety and depression group increased (all P<0.05). Correlation analysis showed that MPO was positively correlated with the score of HADS-total (HADS-t), HADS-anxiety (HADS-a), or HADS-depression (HADS-d), while LXA4 was negatively correlated with HADS-t or HADS-d. Multiple ordinal logistic regression analysis revealed that higher HADS-t score, stable angina, unstable angina, and acute myocardial infarction were the independent impact factors for the elevation of M/L ratio. CONCLUSION: Anxiety and depression may aggravate the inflammatory response in CHD patients. The imbalance between inflammation and anti-inflammation may be part of the mechanism.

The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC.

This study aimed to explore the role and mechanism of felodipine in lung cancer therapy. Murine subcutaneous lung squamous cancer (LUSC) models constructed by KLN-205 cells were utilized to assess the effect of felodipine monotherapy and in combination with the programmed cell death protein 1 antibody (PD1ab) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4ab). Immunohistochemistry analysis was subsequently applied to detect the number of CD8+ T cells and Ki67+ cells. Lastly, a series of in vitro and in vivo experiments were performed to evaluate the effects of felodipine on human LUSC cells and explore the preliminary mechanism underlying felodipine inhibition. The results revealed that felodipine monotherapy exerted a significant inhibitory effect on LUSC growth and synergistic antitumoral activity with PD1ab and CTLA4ab. Meanwhile, immunohistochemistry analysis displayed that felodipine promoted CD8+ T-cell infiltration and downregulated Ki67 expression in tumor cells. Moreover, in vitro and in vivo experiments utilizing human LUSC cells determined that felodipine impaired the proliferative and migratory abilities of cancer cells. In addition, TCGA data analysis uncovered that nuclear factor of activated T cell (NFAT1) expression was positively correlated with overall survival and disease-free survival. Finally, the cell counting kit-8 assay signaled that felodipine might suppress tumor growth by modulating NFAT1.

[An examination of the carbon metabolic pathways in Acinetobacter sp. TAC-1 in the context of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) utilization].

The present study aimed to unravel the carbon metabolism pathway of Acinetobacter sp. TAC-1, a heterotrophic nitrification-aerobic denitrification (HN-AD) strain that utilizes poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as a carbon source. Sodium acetate was employed as a control to assess the gene expression of carbon metabolic pathways in the TAC-1 strain. The results of genome sequencing demonstrated that the TAC-1 strain possessed various genes encoding carbon metabolic enzymes, such as gltA, icd, sucAB, acs, and pckA. KEGG pathway database analysis further verified the presence of carbon metabolism pathways, including the glycolytic pathway (EMP), pentose phosphate pathway (PPP), glyoxylate cycle (GAC), and tricarboxylic acid (TCA) cycle in the TAC-1 strain. The differential expression of metabolites derived from distinct carbon sources provided further evidence that the carbon metabolism pathway of TAC-1 utilizing PHBV follows the sequential process of PHBV (via the PPP pathway)→gluconate (via the EMP pathway)→acetyl-CoA (entering the TCA cycle)→CO2+H2O (generating electron donors and releasing energy). This study is expected to furnish a theoretical foundation for the advancement and implementation of novel denitrification processes based on HN-AD and solid carbon sources.

Transdermal drug delivery via microneedles for musculoskeletal systems.

As the population is ageing and lifestyle is changing, the prevalence of musculoskeletal (MSK) disorders is gradually increasing with each passing year, posing a serious threat to the health and quality of the public, especially the elderly. However, currently prevalent treatments for MSK disorders, mainly administered orally and by injection, are not targeted to the specific lesion, resulting in low efficacy along with a series of local and systemic adverse effects. Microneedle (MN) patches loaded with micron-sized needle array, combining the advantages of oral administration and local injection, have become a potentially novel strategy for the administration and treatment of MSK diseases. In this review, we briefly introduce the basics of MNs and focus on the main characteristics of the MSK systems and various types of MN-based transdermal drug delivery (TDD) systems. We emphasize the progress and broad applications of MN-based transdermal drug delivery (TDD) for MSK systems, including osteoporosis, nutritional rickets and some other typical types of arthritis and muscular damage, and in closing summarize the future prospects and challenges of MNs application.

Endopeptidase O promotes Streptococcus suis immune evasion by cleaving the host- defence peptide cathelicidins.

Streptococcus suis is a zoonotic Gram-positive bacterium that causes invasive infections such as sepsis and meningitis, threatening public health worldwide. For successful establishment of infection, the bacterium should subvert the innate effectors of immune defence, including the cathelicidin family of host-defence peptides that combat pathogenic bacteria by directly disrupting cell membranes and coordinating immune responses. Here, our study shows that an extracellular endopeptidase O (PepO) of S. suis contributes to assisting the bacterium to resist cathelicidin-mediated killing, as the deletion of the pepO gene makes S. suis more sensitive to the human cathelicidin LL-37, as well as its mouse equivalent, mCRAMP. This protease targets and cleaves both LL-37 and mCRAMP, degrading them into shorter peptides with only a few amino acids, thereby abrogating their ability to kill S. suis. By cleaving LL-37 and mCRAMP, PepO impairs their chemotactic properties for neutrophil migration and undermines their anti-apoptosis activity, which is required for prolonging neutrophil lifespan. Also, PepO inhibits the ability of LL-37 and mCRAMP to promote lysosome development in macrophages. Moreover, the loss of PepO attenuates organ injury and decreases bacterial burdens in a murine model of S. suis bacteraemia. Taken together, these data provide novel insights into the role of the intrinsic proteolytic characteristics of PepO in S. suis-host interaction. Our findings demonstrate that S. suis utilizes the PepO protease to cleave cathelicidins, which is an immunosuppressive strategy adopted by this bacterium to facilitate pathogenesis.