Targeting neutrophil elastase is a promising direction for future cancer treatment.

Neutrophil elastase (NE) is a proteolytic enzyme released extracellular during the formation of neutrophil extracellular traps (NETs) through degranulation. In addition to participating in the body's inflammatory response, NE also plays an important role in cancer. It can promote tumor proliferation, migration, and invasion, induce epithelial-mesenchymal transition (EMT), and change the tumor microenvironment (TME) to promote tumor progression. Concurrently, NE promotes systemic treatment resistance by inducing EMT. However, it can also selectively kill cancer cells and attenuate tumor development. Sivelestat is a specific NE inhibitor that can be used in the perioperative period of esophageal cancer patients to reduce the incidence of postoperative complications after esophagectomy. In addition, the combination of sivelestat and trastuzumab can enhance the efficacy of human epidermal growth factor receptor 2(HER 2) positive breast cancer patients. Meanwhile, targeting the human antibody domains and fragments of NE is also a new way to treat cancer and inflammation-related diseases. This review provides valuable insights into the role of NE in cancer treatment. Additionally, we discuss the challenges associated with the clinical application of sivelestat. By shedding light on the promising potential of NE, this review contributes to the advancement of cancer treatment strategies.

Non-Fourier Heat Conduction of Nano-Films under Ultra-Fast Laser.

The ultra-fast laser heating process of nano-films is characterized by an ultra-short duration and ultra-small space size, in which the classical Fourier law based on the hypothesis of local equilibrium is no longer applicable. Based on the Cattaneo-Vernotte (CV) model and the dual-phase-lag (DPL) model, the two-dimensional analytical solutions of heat conduction in nano-films under ultra-fast laser are obtained using the integral transformation method. The results show that there is a thermal wave phenomenon inside the film, which becomes increasingly evident as the elapse of the lag time of the temperature gradient. Moreover, the wave amplitude in the vertical direction is much larger than that in the horizontal direction of the nano-film. By comparing the numerical result of the two models, it is found that the temperature distribution inside the nano-film based on the DPL model is gentler than that of the CV model. Additionally, the temperature distribution in the two-dimensional solution is lower than that in the one-dimensional solution under the same Knudsen number. In the comparison results of the CV model, the maximum peak difference in the thermal wave reaches 75.08 K when the Knudsen number is 1.0. This demonstrates that the horizontal energy carried by the laser source significantly impacts the temperature distribution within the film.

Field investigation of the heat stress in outdoor of healthcare workers wearing personal protective equipment in South China.

Since the advent of coronavirus disease 2019 (COVID-19), healthcare workers (HCWs) wearing personal protective equipment (PPE) has become a common phenomenon. COVID-19 outbreaks overlap with heat waves, and healthcare workers must unfortunately wear PPE during hot weather and experience excessive heat stress. Healthcare workers are at risk of developing heat-related health problems during hot periods in South China. The investigation of thermal response to heat stress among HCWs when they do not wear PPE and when they finish work wearing PPE, and the impact of PPE use on HCWs' physical health were conducted. The field survey were conducted in Guangzhou, including 11 districts. In this survey, HCWs were invited to answer a questionnaire about their heat perception in the thermal environment around them. Most HCWs experienced discomfort in their back, head, face, etc., and nearly 80% of HCWs experienced "profuse sweating." Up to 96.81% of HCWs felt "hot" or "very hot." The air temperature had a significant impact on thermal comfort. Healthcare workers' whole thermal sensation and local thermal sensation were increased significantly by wearing PPE and their thermal sensation vote (TSV) tended towards "very hot." The adaptive ability of the healthcare workers would decreased while wearing PPE. In addition, the accept range of the air temperature (T a) were determined in this investigation. Graphical Abstract.

Human thermal physiological response of wearing personal protective equipment: An educational building semi-open space experimental investigation.

With the outbreak and spread of the COVID-19 epidemic, HCWs are frequently required to wear personal protective equipment (PPE) for nucleic acid sample collection in semi-open transition spaces. Wearing PPE causes significant psychological and physical stress in HCWs. In this study, operative temperature (Top) and wet-bulb globe temperature (WBGT) were used to assess thermal conditions through field experiments, while multiple physiological parameters were measured in the subjects. The results indicated that the subjects showed statistically significant differences in thermal perception and physiological parameters with and without PPE. Using observed increases in heart rate (HR), auditory canal temperature (Tac), mean skin temperature (MST), and end-tidal CO2 pressure, subjects were shown to have an increased metabolic rate and heat storage while wearing PPE. Additionally, a decrease in oxygen concentration was also observed, and this decrease may be linked to fatigue and cognitive impairment. Moreover, HR, MST, and Tac showed a significant linear relationship, which increased with temperature and operative temperature, and the HR response was stronger with PPE than without PPE. The neutral, preferred, and acceptable temperatures were significantly lower with PPE than without PPE, and the deviations for neutral Top/WBGT were 9.5/7.1 °C and preferred Top/WBGT was 2.2/4.0 °C, respectively. Moreover, the upper limits of acceptable WBGT, 29.4 °C with PPE and 20.4 °C without PPE, differed significantly between the two phases. Furthermore, the recorded physiological parameter responses and thermal perception responses of the subjects while wearing PPE indicated that they were at risk of thermal stress. Overall, these results suggest that people who wear PPE should focus on their health and thermal stress. This study provides a reference for the development of strategies to counteract heat stress and improve thermal comfort.

PA-MSHA Regulates PD-L1 Expression in Hepatoma Cells.

BACKGROUND: Programmed death ligand 1 (PD-L1) is expressed in hepatocellular carcinoma (HCC) cells. PD-L1 function and structure are regulated through glycosylation and various signaling pathways. However, the relationship between Pseudomonas aeruginosa mannose sensitive hemagglutinin (PA-MSHA), glycosylation and PD-L1 warrants further study. In this study, we investigated the effects of PA-MSHA on the regulation of mannosyl and N-glycosylation to identify the mechanisms underlying its function. METHODS: PD-L1, ß-catenin, c-Myc, mannosyl, MGAT1 and mannosidase II in HCC were identified by postoperative specimens from the HCC cohort with immunohistochemistry and immunofluorescence. PA-MSHA was used to suppress tumor progression. Alterations to the expression of PD-L1, ß-catenin, c-Myc, MGAT1, and mannosidase II at the gene and protein levels were detected by qRT-PCR and Western blot analysis. Soluble PD-L1 (sPD-L1) were detected using enzyme-linked immunosorbent assay. RESULTS: Mannosyl and mannosidase II expression levels increased, whereas those of MGAT1 decreased in the HCC cells. The glycosylation-related pathway proteins, namely, ß-catenin, c-Myc and PD-L1, had increased expression levels. Moreover, proliferation in the HCC cells was inhibited after PA-MSHA treatment, PD-L1 function was significantly inhibited. Transmission electron microscopy showed that PA-MSHA penetrated into the HCC cytoplasm through the cytomembrane, resulting in apoptosis. Here, PA-MSHA significantly reduced sPD-L1 expression levels in the tumor cells. CONCLUSIONS: PA-MSHA plays the role of a lectin, affecting receptors on the cytomembrane. This strain inhibits mannosyl by suppressing ß-catenin signaling. We hypothesized that PA-MSHA suppresses PD-L1 by: 1. Inhibiting the glycosylation process; and 2. Suppressing ß-catenin and c-Myc, thereby reducing the transcription of this protein.

CTPS1 inhibition suppresses proliferation and migration in colorectal cancer cells.

Colorectal cancer (CRC) is now the third most prevalent tumor and one of the deadliest cancers worldwide, with an increasing prevalence every year. Therefore, we urgently need to understand the mechanisms regulating the progression of colorectal cancer and find potential diagnostic biomarkers. In this study, we performed an analysis using the TCGA and GEO databases to find a molecular biomarker for the diagnosis of CRC, namely CTPS1. The results of this analysis revealed that CTPS1 could promote tumor proliferation and metastasis. Furthermore, bioinformatics analysis revealed that CTPS1 promoted CRC progression through cell cycle and p53 pathways. Further investigation demonstrated that CTPS1 might be involved in the regulation of CCNB1, RRM2, GTSE1, CDK2 and CHEK2 genes. Moreover, PCR confirmed that CTPS1 regulated GTSE1 and CDK2 molecules. Then, western blot was used to verify that CTPS1 promoted the expression of GTSE1 and CDK2 by inhibiting the expression of p53. In summary, we identified an important diagnostic biomarker for CRC, namely CTPS1, and its importance was validated at the cellular level. These results suggest that CTPS1 could serve as a candidate biomarker for CRC and CTPS1 inhibitors may be a potential treatment for CRC.

Experimental investigation of the effects of personal protective equipment on thermal comfort in hot environments.

Since the outbreak of COVID-19, wearing personal protective equipment (PPE) has become increasingly common, especially for healthcare workers performing nucleic acid sample collection. A field experiment and questionnaire survey were conducted in a semi-open transition space of a university building in Guangzhou, southern China. Thirty-two subjects wore PPE to simulate nucleic acid sample collection, during which thermal parameters were recorded and subjective questionnaires were completed. The relationship between thermal sensation and thermal index was analyzed to determine the neutral temperature and comfort temperature zones. Subjects had higher requirements for thermal environment parameters when wearing PPE than when not wearing PPE, and were found to have statistically significant differences in thermal perception when wearing and not wearing PPE. Wearing PPE significantly raised the subjects' thermal and humidity sensations and restricted their airflow. Wearing PPE resulted in thermal discomfort for the subjects and a high unacceptability rate for environmental thermal parameters. The subjects wore PPE for an acceptable duration of approximately 1.5 h. The neutral operative temperatures were significantly lower when wearing PPE than when not wearing PPE, and the deviation from the neutral temperature was 9.7 °C. The neutral operative temperature was 19.5 °C and the comfort temperature zone was 17.4-21.5 °C when subjects wore PPE, demonstrating that subjects who wore PPE preferred lower temperatures. These results suggest that people who wear PPE for work, especially outdoors, should receive more attention to ensure thermal comfort and safety.

Investigation of the effects of face masks on thermal comfort in Guangzhou, China.

Wearing masks to study and work places has become a daily protective measure during the COVID-19 pandemic. In the summer of 2021, environmental parameters were monitored, and students in a university library in Guangzhou, China, were surveyed to analyze the possible symptoms of wearing masks for a long time, and to assess the sensitivity of various body parts to the environmental parameters. Concurrently, the preference of subjects wearing masks for various environmental parameters was also analyzed. Additionally, the relationship between thermal sensation and thermal index was analyzed to identify acceptable and comfortable temperature ranges. The expected duration of wearing masks was counted. Subjects wearing masks had greater requirements for environmental comfort, and reported increased thermal discomfort of the face and head, compared to those without masks. More than 70% of the subjects wearing masks reported that they experienced discomfort on their faces. Among the subjects who experienced discomfort, 62.7% reported that facial fever was the main symptom; while some reported symptoms of dyspnea (25.4%) and rapid heartbeat (9.1%). More than 75% of the subjects were expected to wear masks for 2.0 h or less. Evaluation of environmental thermal sensation, including overall, facial, and head thermal sensation, differed among subjects who wore and did not wear masks. The indexes of neutral Operative temperature/Standard Effective Temperature (T op /SET*) and preferred T op /SET* were lower among subjects with masks than among those without masks. The neutral T op /SET* deviation was 0.3 °C, and the preferred T op /SET* deviation was 0.5 °C. Additionally, the acceptable and comfortable temperature zones differed between the two cases. The subjects who wore masks preferred colder temperatures. These findings indicated that the environmental parameters should be adjusted to improve the thermal comfort of the human body while wearing masks in work or study places.

Measurement of soluble PD-1 and soluble PD-L1 as well as PD-L1 and PD-1 from perioperative patients with gastric carcinoma.

BACKGROUND: Till now, no experiment has been performed to detect programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1), soluble PD-L1/soluble PD-1 simultaneously in perioperative patients of gastric carcinoma. Our experiment aims at determining the clinical significance and possible mechanism of soluble PD-L1/soluble PD-1 in gastric carcinoma. METHODS: Thirty patients undergone gastrectomy were selected as the experimental group. Tissue's programmed death ligand 1 and peripheral programmed death 1 were detected using immunofluorescence and flow cytometry. Soluble PD-L1 and soluble PD-1 were detected using enzyme-linked immunosorbent assay. RESULTS: First, preoperative programmed death 1 was higher than control group and decreased to normal post-operatively. Preoperatively ,elevated levels of programmed death 1 on cluster of differentiation (CD)4 T cells indicated less lymphatic metastasis (P < 0.01) and small tumor volume (P < 0.01); elevated programmed death 1 of CD8 T cells indicated big tumor volume (P < 0.01) and well histological differentiation (P < 0.01). Second, preoperative soluble PD-L1 and soluble PD-1 are lower than in control group. Post-operatively, the soluble PD-1 rose to normal, but the soluble PD-L1 showed no change. Third, programmed death ligand 1 can be observed in carcinoma tissue. Fourth, the area under the curve of soluble PD-1 (0.675) for diagnosis was worse than that of soluble PD-L1 (0.885). Kaplan-Meier analysis showed that soluble PD-1 < 245.26 pg/ml in post-operative serum predicted a poor prognosis (overall survival percentage: 60%) at 2 years (P < 0.05). Multivariate analysis revealed that carcinoembryonic antigen (>5 ng/l) and soluble PD-1 after gastrectomy (>245.26 pg/ml) were independent prognostic factors for overall survival (hazard ratio: 20.812, 95% confidence interval: 1.217-355.916, P = 0.036; hazard ratio: 0.028, 95% confidence interval: 0.001-0.786, P = 0.036, respectively). CONCLUSIONS: We propose that soluble PD-1 combined with programmed death ligand 1 are effective not only in protecting T cells from the adhesion by programmed death ligand 1 but also in preventing the occurrence and the development of tumor as well. Through multivariate analysis, we found that soluble PD-1 was an independent protective factor for post-operative prognosis of gastric carcinoma patients, which indirectly verified the vital function of soluble PD-1. Soluble PD-1 might be promising predictive biomarkers for the diagnosis and prognosis of gastric carcinoma patients.

Preparation of 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives and their activity against DOT1L.

From a readily available 5-C-Me ribofuranoside, we have realized a reliable route to valuable 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives at gram scale with confirmed stereochemistry. These adenosine derivatives are useful starting materials for the preparation of 5'-deoxy-5'-amino-5'-C-methyl adenosine derivatives with higher complexity. From one of the new adenosine derivatives, some 5'-deoxy-5'-amino-5'-C-methyl adenosine DOT1L inhibitors were prepared in several steps. Data from DOT1L assay indicated that additional 5'-C-Me group improved the enzyme inhibitory activity.