Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

The impact of hypertension on clinical manifestations of Omicron variant BA.1 infection in adult patients.

COVID-19 caused by Omicron BA.1 has resulted in a global humanitarian crisis. In this COVID-19 pandemic era, hypertension has been receiving increased attention. Omicron BA.1 infection combined with hypertension created a serious public health problem and complicated the treatment and prognosis of COVID-19. The aim of our study was to assess the implications of hypertension for the clinical manifestations of adult patients (APs) infected with Omicron BA.1. This single-center retrospective cohort study enrolled consecutive COVID-19 APs, who were admitted to Tianjin First Central Hospital from 01 August 2022 to 30 November 2022. All included APs were divided into two groups: hypertension and non-hypertension group. The APs' baseline demographic, laboratory, clinical, and radiological characteristics were collected and analyzed. Of 512 APs admitted with PCR proven COVID-19, 161 (31.45%) APs had comorbid hypertension. Hypertension APs have older age, higher body mass index, lower Ct-values of the viral target genes at admission, and longer hospital stay than non-hypertension APs. Furthermore, hypertension aggravates the clinical classification, impairs liver, kidney, and myocardium function, and abnormalizes the coagulation system in Omicron BA.1- infected APs. Moreover, hypertension elevates inflammation levels and lung lesion involvement while weakened virus-specific IgM level in APs with Omicron BA.1 infection. Hypertension APs tend to have worse clinical conditions at baseline than those non-hypertension APs. This study indicates that hypertension is a contributor to the poor clinical manifestations of Omicron BA.1-infected APs and supports that steps to control blood pressure should be a vital consideration for reducing the burden of Omicron BA.1 infection in hypertension individuals. IMPORTANCE: This study provided inclusive insight regarding the relationship between hypertension and Omicron BA.1 infection and supported that hypertension was an adverse factor for COVID-19 APs. In conclusion, this study showed that hypertension was considered to be associated with severe conditions, and a contributor to poor clinical manifestations. Proper medical management of hypertension patients is an imperative step in mitigating the severity of Omicron BA.1 variant infection.

Low-temperature NH3 abatement via selective oxidation over a supported copper catalyst with high Cu+ abundance.

Selective catalytic NH3-to-N2 oxidation (NH3-SCO) is highly promising for abating NH3 emissions slipped from stationary flue gas after-treatment devices. Its practical application, however, is limited by the non-availability of low-cost catalysts with high activity and N2 selectivity. Here, using defect-rich nitrogen-doped carbon nanotubes (NCNT-AW) as the support, we developed a highly active and durable copper-based NH3-SCO catalyst with a high abundance of cuprous (Cu+) sites. The obtained Cu/NCNT-AW catalyst demonstrated outstanding activity with a T50 (i.e. the temperature to reach 50% NH3 conversion) of 174°C in the NH3-SCO reaction, which outperformed not only the Cu catalyst supported on N-free O-functionalized CNTs (OCNTs) or NCNT with less surface defects, but also those most active Cu catalysts in open literature. Reaction kinetics measurements and temperature-programmed surface reactions using NH3 as a probe molecule revealed that the NH3-SCO reaction on Cu/NCNT-AW follows an internal selective catalytic reaction (i-SCR) route involving nitric oxide (NO) as a key intermediate. According to mechanistic investigations by X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray absorption spectroscopy, the superior NH3-SCO performance of Cu/NCNT-AW originated from a synergy of surface defects and N-dopants. Specifically, surface defects promoted the anchoring of CuO nanoparticles on N-containing sites and, thereby, enabled efficient electron transfer from N to CuO, increasing significantly the fraction of SCR-active Cu+ sites in the catalyst. This study puts forward a new idea for manipulating and utilizing the interplay of defects and N-dopants on carbon surfaces to fabricate Cu+-rich Cu catalysts for efficient abatement of slip NH3 emissions via selective oxidation.

Prognostic predictive value of urothelial carcinoma of the bladder after TURBT based on multiphase CT radiomics.

OBJECTIVE: To investigate multiphase computed tomography (CT) radiomics-based combined with clinical factors to predict overall survival (OS) in patients with bladder urothelial carcinoma (BLCA) who underwent transurethral resection of bladder tumor (TURBT). METHODS: Data were retrospectively collected from 114 patients with primary BLCA from February 2016 to February 2018. The regions of interest (ROIs) of the plain, arterial, and venous phase images were manually segmented. The Cox regression algorithm was used to establish 3 basic models for the plain phase (PP), arterial phase (AP), and venous phase (VP) and 2 combination models (AP + VP and PP + AP + VP). The highest-performing radiomics model was selected to calculate the radiomics score (Rad-score), and independent risk factors affecting patients' OS were analyzed using Cox regression. The Rad-score and clinical risk factors were combined to construct a joint model and draw a visualized nomogram. RESULTS: The combined model of PP + AP + VP showed the best performance with the Akaike Information Criterion (AIC) and Consistency Index (C-index) in the test group of 130.48 and 0.779, respectively. A combined model constructed with two independent risk factors (age and Ki-67 expression status) in combination with the Rad-score outperformed the radiomics model alone; AIC and C-index in the test group were 115.74 and 0.840, respectively. The calibration curves showed good agreement between the predicted probabilities of the joint model and the actual (p < 0.05). The decision curve showed that the joint model had good clinical application value within a large range of threshold probabilities. CONCLUSION: This new model can be used to predict the OS of patients with BLCA who underwent TURBT.

Investigation of bioactive compounds and their correlation with the antioxidant capacity in different functional vinegars.

There are complex and diverse substances in traditional vinegars, some of which have been identified as biologically active factors, but the variety of functional compounds is currently restricted. In this study, it was aimed to determine the bioactive compounds in 10 typical functional vinegars. The findings shown that total flavonoids (0.21-7.19 mg rutin equivalent/mL), total phenolics (0.36-3.20 mg gallic acid equivalent/mL), and antioxidant activities (DPPH: 3.17-47.63 mmol trolox equivalent/L, ABTS: 6.85-178.29 mmol trolox equivalent/L) varied among different functional vinegars. In addition, the concentrations of the polysaccharides (1.17-44.87 mg glucose equivalent/mL) and total saponins (0.67-12.46 mg oleanic acid equivalent/mL) were determined, which might play key role for the function of tested vinegars. A total of 8 organic acids, 7 polyphenol compounds and 124 volatile compounds were measured and tentatively identified. The protocatechuic acid (4.81-485.72 mg/L), chlorogenic acid (2.69-7.52 mg/L), and epicatechin (1.18-97.42 mg/L) were important polyphenol compounds in the functional vinegars. Redundancy analysis indicated that tartaric acid, oxalic acid and chlorogenic acid were significantly positively correlated with antioxidant capacity. Various physiologically active ingredients including cyclo (Pro-Leu), cyclo (Phe-Pro), cyclo (Phe-Val), cyclo (Pro-Val), 1-monopalmitin and 1-eicosanol were firstly detected in functional vinegars. Principle component analysis revealed that volatiles profile of bergamot Monascus aromatic vinegar and Hengshun honey vinegar exhibited distinctive differences from other eight vinegar samples. Moreover, the partial least squares regression analysis demonstrated that 11 volatile compounds were positively correlated with the antioxidant activity of vinegars, which suggested these compounds might be important functional substances in tested vinegars. This study explored several new functionally active compounds in different functional vinegars, which could widen the knowledge of bioactive factor in vinegars and provide new ideas for further development of functional vinegar beverages.

Synthesis, characterization, and sensitivity tests of La0.8Ba0.1Bi0.1FeO3 nanoparticles towards a few parts-per-billion of acetone gas.

In the present paper, the La0.8Ba0.1Bi0.1FeO3 powders were synthesized via the auto-combustion method. The optical, the positron annihilation spectroscopy and the gas sensing properties of our sample were investigated simultaneously. FTIR spectrum revealed the antisymmetric deformation vibrations of the Fe-O and Fe-O-Fe bonds inside the octahedron FeO6. The optical bandgap (Egap) of the La0.8Ba0.1Bi0.1FeO3 compound was found to be equal to 2.23 eV. We confirmed by the positron annihilation studies, the existence of open volume defects and vacancy sized defects, at the grain/interfaces between vacancy clusters and grains at the interfaces intersection (triple-lines). Notably, the La0.8Ba0.1Bi0.1FeO3 perovskite exhibits an excellent response toward acetone gas, with ultra-fast response and recovery times to some parts-per-billion (ppb) of this tested gas.

Shift work promotes adipogenesis via cortisol-dependent downregulation of EGR3-HDAC6 pathway.

The disruption of circadian rhythms caused by long-term shift work can cause metabolic diseases such as obesity. Early growth response 3 (EGR3) is a member of early growth response (EGR) family, which is involved in several cellular responses, had been reported as a circadian rhythm gene in suprachiasmatic nucleus. In this research, EGR3 was found to be widely expressed in the different tissue of human and mice, and downregulated in adipose tissue of obese subjects and high-fat diet mice. Moreover, EGR3 was found negatively regulated by cortisol. In addition, EGR3 is a key negative modulator of hADSCs and 3T3-L1 adipogenesis via regulating HDAC6, which is a downstream target gene of EGR3 and a negative regulator of adipogenesis and lipogenesis. These findings may explain how circadian rhythm disorder induced by shift works can cause obesity. Our study revealed a potential therapeutic target to alleviate metabolic disorders in shift workers and may provide better health guidance to shift workers.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Laquinimod attenuates oxidative stress-induced mitochondrial injury and alleviates intervertebral disc degeneration by inhibiting the NF-κB signaling pathway.

BACKGROUND: Low back pain (LBP) caused by intervertebral disc degeneration (IVDD) is a significant global health concern. It is necessary to investigate the underlying pathological mechanisms leading to IVDD and develop precise treatment strategies for this condition. Considering the well-established anti-inflammatory properties and ability to reduce oxidative stress in various diseases, for the first time we aim to explore the potential of Laquinimod in alleviating IVDD. METHODS: We used hydrogen peroxide (H2O2) to simulate the oxidative stress microenvironment in IVDD, and Laquinimod for intervention purposes. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assay were used to measure the expression levels of inflammatory cytokines, catabolic enzymes, and markers of extracellular matrix (ECM) synthesis in nucleus pulposus (NP) cells. In addition, dichlorofluorescin-diacetate (DCFH-DA) and JC-1 fluorescent probes, flow cytometry analysis, and qRT-PCR were used to measure mitochondrial function and apoptosis in NP cells under conditions of oxidative stress. An acupuncture-induced rat model of IVDD was established to further evaluate the efficacy of Laquinimod in alleviating IVDD in vivo. RESULTS: Our findings showed that Laquinimod significantly reduced the oxidative stress-induced inflammatory response in NP cells, downregulated the expression of catabolic enzymes, and markedly enhanced ECM degradation by inhibiting the NF-κB signaling pathway. The administration of Laquinimod concurrently improved the mitochondrial functional state and reduced apoptosis in NP cells. Additionally, in vivo experiments in rats showed that Laquinimod significantly alleviated acupuncture-induced IVDD. CONCLUSIONS: Collectively, the findings of this study provide new insights into the therapeutic potential of Laquinimod as a treatment for oxidative stress-induced IVDD.

Anti-Inflammatory Effect of Columbianadin against D-Galactose-Induced Liver Injury In Vivo via the JAK2/STAT3 and JAK2/p38/NF-κB Pathways.

Angelicae pubescentis radix (APR) has been traditionally used for thousands of years in China to treat rheumatoid arthritis (RA), an autoimmune disorder. As the main active coumarin of APR, columbianadin (CBN) exhibits a significant anti-inflammatory effect in vitro. However, the anti-inflammatory activity and underlying mechanism of CBN in vivo remain unclear. This work aimed to elucidate the anti-inflammatory activity of CBN in vivo and its related signaling pathways in a D-Gal-induced liver injury mouse model. Analysis of biochemical indices (ALT and AST) and pro-inflammatory cytokines (IL-1ß and IL-6) in serum indicated that CBN significantly ameliorated D-Gal-induced liver injury. CBN treatment also significantly increased the activities of antioxidant enzymes (SOD, CAT, GPx), and decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in liver tissue. Liver histology revealed that CBN treatment reduced hepatic inflammation. Western blot analysis indicated that CBN down-regulates the expression of phosphorylated JAK2, STAT3, MAPK, and NF-κB in the related signaling pathways. These findings support the traditional use of APR as a remedy for the immune system, and indicate that the JAK2/STAT3 and JAK2/p38/NF-κB signaling pathways may be important mechanisms for the anti-inflammatory activity of CBN in vivo.

Characteristics of sub-micron aerosols above the urban canopy in Beijing during warm seasons.

To understand the characteristics of atmospheric pollution above the urban canopy in warm seasons, the characteristics of sub-micron aerosol (PM1) was studied based on high-altitude observations at the Beijing 325 m meteorological tower. The PM1 at 260 m was 34, 29 and 21 µg m-3 in May 2015, June 2015, and June 2017, respectively, indicating a reduction in PM1 pollution above the urban canopy. Meanwhile, an overall decrease was also observed in the concentrations of all PM1 chemical species (excluding Chl and BC) and organic aerosol (OA) factors. Previous instances of heavy haze in Beijing often coincided with high humidity and stagnant weather conditions. However, the heightened pollution episodes in June 2017 were accompanied by high wind speeds and low relative humidity. Compared to May 2015, the contribution of secondary components to PM1 in June 2017 was more prominent, with the total proportion of SNA (sulfate, nitrate, and ammonium) and more-oxidized oxygenated OA (MO-OOA) to PM1 increased by approximately 10 %. Secondary species of NH4NO3, (NH4)2SO4, and MO-OOA, as well as black carbon, collectively contributed the vast majority of aerosol extinction coefficient (bext), with the four species contributing a total of ≥96 % to bext at 260 m. Hydrocarbon-like OA, cooking OA, and less-oxidized oxygenated OA have undergone significant reductions, so continued emphasis on controlling local sources to reduce these three aerosol species and addressing regional sources to further mitigate overall aerosol species is imperative. In lower pollution situation, the diurnal variation of PM was smoother, and its pollution sources were more regionally uniform, which might be attributed to the reduced diversity and complexity in the physical and chemical processes in air pollution.

Beta-variant recombinant booster vaccine elicits broad cross-reactive neutralization of SARS-CoV-2 including Omicron variants.

Background: SARS-CoV-2 Omicron lineage contains variants with multiple sequence mutations relative to the ancestral strain particularly in the viral spike gene. These mutations are associated inter alia with loss of neutralization sensitivity to sera generated by immunization with vaccines targeting ancestral strains or prior infection with circulating (non-Omicron) variants. Here we present a comparison of vaccine formulation elicited cross neutralization responses using two different assay readouts from a subpopulation of a Phase II/III clinical trial. Methods: Human sera from a Phase II/III trial (NCT04762680) was collected and evaluated for neutralizing responses to SARS-CoV-2 spike antigen protein vaccines formulated with AS03 adjuvant, following a primary series of two-doses of ancestral strain vaccine in individuals who were previously unvaccinated or as an ancestral or variant strain booster vaccine among individuals previously vaccinated with the mRNA BNT162b2 vaccine. Results: We report that a neutralizing response to Omicron BA.1 is induced by the two-dose primary series in 89% of SARS-CoV-2-seronegative individuals. A booster dose of each vaccine formulation raises neutralizing antibody titers that effectively neutralizes Omicron BA.1 and BA.4/5 variants. Responses are highest after the monovalent Beta variant booster and similar in magnitude to human convalescent plasma titers. Conclusion: The findings of this study suggest the possibility to generate greater breadth of cross-neutralization to more recently emerging viral variants through use of a diverged spike vaccine in the form of a Beta variant booster vaccine.

Rational control of the typical surface defects of hybrid perovskite using tetrahexylammonium iodide.

There are numerous defects existing on the surface and grain boundary of perovskite, which adversely affect the performance and stability of perovskite solar cell devices. Systematic first-principles calculations show that the I vacancy (VI), Pb vacancy (VPb), Pb-I antisite (PbI), and I-Pb antisite (IPb) defects can significantly affect the electronic properties of the surface of formamidinium lead triiodide (FAPbI3); in particular the VPb, PbI and IPb surface defects can introduce defect energy levels in the band gap. Tetrahexylammonium iodide (THAI) that is strongly adsorbed on the (1 0 0) surface of FAPbI3 by forming Pb-I coordination bonds and I⋯H hydrogen bonds could eliminate or reduce the defect states near the band edge or in the band gap by transferring electrons between THAI and the surface of FAPbI3. In particular, the defect states introduced by VPb could be completely eliminated after the adsorption of THAI. This study shows an in-depth understanding of the influence of defects on the electronic properties of the surface of FAPbI3, as well as the passivation mechanism of organic salts on the surface defects of perovskite.

A modified geometric technique to increase peri-implant keratinized mucosa.

OBJECTIVE: The free gingival graft (FGG) has been identified as the most effective method for increasing keratinized mucosa width (KMW). However, the challenge emerges in cases of extensive keratinized mucosa deficiency, where efficient utilization of the patient's limited keratinized tissue to achieve optimal results is crucial. This article introduces a modified geometric technique to address this clinical issue. CLINICAL CONSIDERATIONS: Utilizing geometric principles, the modified technique involves dividing the rectangular graft into two triangular or trapezoidal sections, which are then reassembled to form an approximate diamond shape. Through strategic cut and splice, the graft is reshaped to suit the recipient site. CONCLUSION: Preliminary observations in cases employing the modified geometric technique have increased the KMW around implants. This method enhances graft utilization and offers a viable clinical option for surgical plans aimed at widening keratinized mucosa in instances of large-area KMW deficiency. CLINICAL SIGNIFICANCE: This article proposed a modified method to increase KMW, which may be an optimal choice for patients with insufficient KMW in large area, avoiding the waste of limited graft, decreasing patient morbidity, and effectively widening keratinized mucosa.

Design and optimization of a multidirectional photodetector in optoelectronic integration.

We have introduced and demonstrated a three-dimensional, multidirectional photodetector (PD) made of germanium for optoelectronic integration (OEI) systems. Building upon the fundamental physical principles of PDs, we focused on the design aspects of structure, dimensions, and doping. This led to the development of an integrated chip-level PD capable of discerning light from four different directions. Simulation verification confirmed that the key performance parameters of the four equivalent PDs meet the specified requirements. Importantly, we have identified the device's ability and strategy to evaluate light signals from different directions, as well as the impact of fluctuations in light intensity on the accuracy of the judgments. In-depth investigations into the effects of external bias, doping concentration, and doping region have been conducted to further optimize parameters, enhancing the performance of the proposed device. Overall, the current work will help improve the efficiency of PD and enhance the integration of future OEI chips.

Effect of liver cancer on the accumulation and hepatobiliary transport of per- and polyfluoroalkyl substances.

In this study, we examined the distribution of per- and polyfluoroalkyl substances (PFASs) in liver and bile tissues from the patients with liver cancer (n = 202) and healthy controls (n = 30), and calculated the hepatobiliary transport efficiency (TB-L) of PFASs. Among 21 PFASs, 13 PFASs were frequently detected in the liver (median: 8.80-16.3 ng/g) and bile (median: 11.03-14.26 ng/mL) samples. PFAS concentrations in liver were positively correlated with age, with higher levels of PFASs in the older. Variance analysis showed that gender and BMI (Body Mass Index) have an important impact on the distribution of PFASs. A U-shaped trend in TB-L of PFASs with the increasing of carbon chain length was found for the first time, and the TB-L of most PFASs in the control was higher than that of those in cases (p < 0.05), suggesting that hepatic injury would affect their transport. PFASs were positively associated with liver injury biomarkers, including γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), and total bilirubin (TB) levels (p < 0.05). This is the first study on examining the hepatobiliary transport characteristics of PFASs, which may help understand the connection between PFAS accumulation and liver cancer risk.