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With the growing dependence on lithium-ion batteries, there is an urgent need to understand the potential developmental toxicity of LiPF6, a key component of these batteries. Although lithium's toxicity is well-established, the biological toxicity of LiPF6 has been minimally explored. This study leverages the zebrafish model to investigate the developmental impact of LiPF6 exposure. We observed morphological abnormalities, reduced spontaneous movement, and decreased hatching and swim bladder inflation rates in zebrafish embryos, effects that intensified with higher LiPF6 concentrations. Whole-mount in situ hybridization demonstrated that the specific expression of the swim bladder outer mesothelium marker anxa5b was suppressed in the swim bladder region under LiPF6 exposure. Transcriptomic analysis disclosed an upregulation of apoptosis-related gene sets. Acridine orange staining further supported significant induction of apoptosis. These findings underscore the environmental and health risks of LiPF6 exposure and highlight the necessity for improved waste management strategies for lithium-ion batteries. [ABSTRACT FROM AUTHOR]

Objective To investigate the mechanism of Qiangxin Decoction treating chronic heart failure(CHF) by regulating miR-125b-5p and thus inhibiting the expression of nuclear factor-κB (NF-κB)-mediated inflammatory factors in order to protect the cardiovascular endothelial progenitor cells. Methods According to the random number table method, 42 SPF-grade SD rats were divided into the control group, the model group, the Qiangxin Decoction low-dose group (7.45 g/kg), the Qiangxin Decoction medium-dose group (14.90 g/kg), the Qiangxin Decoction high-dose group (29.80 g/kg), and the sacubitril valsartan group (10.42 mg/kg), with 7 rats in each group. Except for the control group, the CHF model was established by ligating the left anterior descending branch of the coronary artery in each group. Two days after modeling, the rats were treated with the corresponding drugs by gavage for 28 days. Cardiac function indexes, including left ventricular end-diastolic internal diameter (LVEDd), left ventricular end-systolic internal diameters (LVEDs), and left ventricular ejection fraction (LVEF), were examined by cardiac ultrasound examination, and the pathological changes in the myocardial tissue of the left ventricle of the rats were observed by HE staining. Myocardial fibrosis was observed in each group by Masson staining. Fluorescence in situ hybridization (FISH) was performed to determine the expression of miR-125b-5p in endothelial progenitor cells of the left ventricular myocardial tissue. The protein expressions of brain-derived neurotrophic factor (BDNF), NF-κB p65 and p-NF-κB p65 in the left ventricular myocardial tissue were detected by Western blotting. Enzyme-linked immunosorbent assay was used to detect the expression of inflammatory factor tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Results Compared with the control group, LVEDd and LVEDs were elevated and LVEF was reduced in the model group; the pathological damage of myocardial tissue was severe with abnormal changes in the tissue structure, striated muscle became fuzzy, and cardiomyocytes were disordered in their arrangement and partially denatured and necrotic; blue collagen fibers and mucus deposition in the myocardial tissues were increased; the average optical density of miR-125b-5p was increased in the left ventricular myocardial tissue; the protein expression of BDNF was decreased, and the ratio of p-NF-κB p65/NF-κB p65 was increased; the contents of TNF-α, IL-1β, and IL-6 were significantly increased (P<0.05). Compared with the model group, LVEDd and LVEDs were reduced, and LVEF was increased in the Qiangxin Decoction medium-, high-dose groups and the sacubitril valsartan group; the pathological damage of myocardial tissues in the left ventricle was improved, with clear striated muscle, neat and orderly arrangement of cardiomyocytes, and reduction of cellular necrosis; blue collagen fibers and mucus deposition were reduced, and myocardial fibrosis was significantly reduced; the average optical density of miR-125b-5p in the left ventricular myocardial tissue was significantly reduced; the protein expression of BDNF was increased, and the ratio of p-NF-κB p65/NF-κB p65 was reduced; the contents of TNF-α, IL-1β, and IL-6 were significantly reduced (P<0.05). Conclusion Qiangxin Decoction can reduce miR-125b-5p expression, inhibit the activation of NF-κB pathway, reduce the expression of the pro-inflammatory factors TNF-α, IL-1β, and IL-6, attenuate the myocardial inflammatory response, pathological injury and reduce myocardial fibrosis, ultimately protect the cardiovascular endothelium, and improve cardiac function to treat CHF. [ABSTRACT FROM AUTHOR]

To encourage the building of a development route for ecological civilization construction which commensurates with China's unique national conditions, early demonstration and pilot ecological civilization zones should be built. This study aims to investigate the effects of ecological civilization construction policies on regional total factor productivity, green total factor productivity, and the methods of action by using panel data from 30 provinces in Mainland China from 2005 to 2020. Our findings indicate that the pilot eco-civilization policies have a more significant effect on the promotion of green total factor production, while the effect on total factor productivity is average. Furthermore, the main purpose of the ecological civilization construction pilot is to improve the level of green innovation, optimise the industrial structure and promote the allocation of factors to achieve a win-win situation for regional economic development and green benefits. Moreover, under different levels of economic growth, the pilot eco-civilization policies have a more significant effect on the promotion of green total factor at various stages of economic growth and industrialization. There are also clear discrepancies in how well ecological civilization construction programmes are implemented. Thus, in order to support high-quality regional economic development, it is crucial to continue to advance and promote the pilot eco-civilization initiatives. [ABSTRACT FROM AUTHOR]

CD8+ T cells are major components of adaptive immunity and confer robust protective cellular immunity, which requires adequate T-cell numbers, targeted migration, and efficient T-cell proliferation. Altered CD8+ T-cell homeostasis and impaired proliferation result in dysfunctional immune response to infection or tumorigenesis. However, intrinsic factors controlling CD8+ T-cell homeostasis and immunity remain largely elusive. Here, we demonstrate the prominent role of Brd4 on CD8+ T cell homeostasis and immune response. By upregulating Myc and GLUT1 expression, Brd4 facilitates glucose uptake and energy production in mitochondria, subsequently supporting naïve CD8+ T-cell survival. Besides, Brd4 promotes the trafficking of naïve CD8+ T cells partially through maintaining the expression of homing receptors (CD62L and LFA-1). Furthermore, Brd4 is required for CD8+ T cell response to antigen stimulation, as Brd4 deficiency leads to a severe defect in clonal expansion and terminal differentiation by decreasing glycolysis. Importantly, as JQ1, a pan-BRD inhibitor, severely dampens CD8+ T-cell immune response, its usage as an anti-tumor agent or latency-reversing agent for human immunodeficiency virus type I (HIV-1) should be more cautious. Collectively, our study identifies a previously-unexpected role of Brd4 in the metabolic regulation of CD8+ T cell-mediated immune surveillance and also provides a potential immunomodulation target. [ABSTRACT FROM AUTHOR]

The reprogramming of lipid metabolism serves an important role in occurrence and development of liver cancer. Fatty acid hydroxylase domain containing 2 (FAXDC2) is a hydroxylase involved in the synthesis of cholesterol and sphingomyelin and downregulated in various types of cancer. There are no reports on the relationship between FAXDC2 and liver carcinogenesis. The present study used multiple portals and publicly available tools to explore its correlation with liver cancer. The results showed that the expression of FAXDC2 decreased in liver cancer and the methylation level near the promoter increased. Patients with liver cancer and with low expression of FAXDC2 had a poor prognosis. Gain of function and loss of function strategies were performed to evaluate its roles in liver cancer cells. CCK-8 assay showed that overexpression of FAXDC2 inhibited the viability of liver cancer cells (HepG2). Flow cytometry analysis indicated that HepG2 cells with overexpressing FAXDC2 showed an S phase arrest, associated with cyclin-dependent kinase 2 decreased. Transwell experiments showed that increasing FAXDC2 inhibited HepG2 cell invasion ability, accompanied by the upregulation of E-cadherin. Notably, knockdown of FAXDC2 had no significant effect on cell cycle and invasion functions. Based on the cBioPortal platform, FAXDC2 was predicted to closely correlate to the ERK signal in tumorigenesis. Western blotting results showed that overexpression of FAXDC2 decreased the phosphorylation level of ERK in liver cancer cells. The present study first identified FAXDC2 as a liver cancer suppressor, which might inhibit the proliferation and invasion of liver cancer cells through the mechanism associated with ERK signaling. The present study provided a possible new target for the diagnosis and treatment of liver cancer. [ABSTRACT FROM AUTHOR]

CD8 + T cells are major components of adaptive immunity and confer robust protective cellular immunity, which requires adequate T-cell numbers, targeted migration, and efficient T-cell proliferation. Altered CD8 + T-cell homeostasis and impaired proliferation result in dysfunctional immune response to infection or tumorigenesis. However, intrinsic factors controlling CD8 + T-cell homeostasis and immunity remain largely elusive. Here, we demonstrate the prominent role of Brd4 on CD8 + T cell homeostasis and immune response. By upregulating Myc and GLUT1 expression, Brd4 facilitates glucose uptake and energy production in mitochondria, subsequently supporting naïve CD8 + T-cell survival. Besides, Brd4 promotes the trafficking of naïve CD8 + T cells partially through maintaining the expression of homing receptors (CD62L and LFA-1). Furthermore, Brd4 is required for CD8 + T cell response to antigen stimulation, as Brd4 deficiency leads to a severe defect in clonal expansion and terminal differentiation by decreasing glycolysis. Importantly, as JQ1, a pan-BRD inhibitor, severely dampens CD8 + T-cell immune response, its usage as an anti-tumor agent or latency-reversing agent for human immunodeficiency virus type I (HIV-1) should be more cautious. Collectively, our study identifies a previously-unexpected role of Brd4 in the metabolic regulation of CD8 + T cell-mediated immune surveillance and also provides a potential immunomodulation target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Peng, Zhang, Ma, Zhou, Wu, Song, Yuan, Chen, Li, Wang, Huang, Qiao, Xia, Liu, Liu, Zhang, He, Pan, Xu and Zhang.)

Background: In the tumor microenvironment, tumor cells are able to suppress antitumor immunity by competing for essential nutrients, including amino acids. However, whether amino acid depletion modulates the activity of CD8 + tumor-infiltrating lymphocytes (TILs) is unclear., Method: In this study, we evaluated the roles of amino acids and the Rag complex in regulating mammalian target of rapamycin complex 1 (mTORC1) signaling in CD8 + TILs., Results: We discovered that the Rag complex, particularly RagD, was crucial for CD8 + T-cell antitumor immunity. RagD expression was positively correlated with the antitumor response of CD8 + TILs in both murine syngeneic tumor xenografts and clinical human colon cancer samples. On RagD deficiency, CD8 + T cells were rendered more dysfunctional, as demonstrated by attenuation of mTORC1 signaling and reductions in proliferation and cytokine secretion. Amino acids maintained RagD-mediated mTORC1 translocation to the lysosome, thereby achieving maximal mTORC1 activity in CD8 + T cells. Moreover, the limited T-cell access to leucine (LEU), overshadowed by tumor cell amino acid consumption, led to impaired RagD-dependent mTORC1 activity. Finally, combined with antiprogrammed cell death protein 1 antibody, LEU supplementation improved T-cell immunity in MC38 tumor-bearing mice in vivo., Conclusion: Our results revealed that robust signaling of amino acids by RagD and downstream mTORC1 signaling were crucial for T-cell receptor-initiated antitumor immunity. The characterization the role of RagD and LEU in nutrient mTORC1 signaling in TILs might suggest potential therapeutic strategies based on the manipulation of RagD and its upstream pathway., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: To investigate the relationship between the subjective sensation of nasal obstruction and the corresponding objective parameters of acoustic rhinometry., Method: Three hundred and sixty-five patients with nasal diseases were divided into two groups: one group included 220 cases with nasal obstruction, and the second group of 145 cases without nasal obstruction. Seventy healthy adults were selected as control. Each one were assessed for nasal minimal cross-sectional area (NMCA), volume of nasal cavity (NV), nasal airway resistance (NAR) and distance of the minimal cross section area from the nostril (DCAN) by using acoustic rhinometry, and the subjective test were performed using the VAS scores. The results were statistically analyzed., Result: NV, DCAN and NAR had a significant difference between nasal obstruct group and control group (P < 0.05). The VAS score had linear correlation with NMCA, NV, DCAN and NAR, and the correlation coefficient were R(NAR) = 0.7385, R(NV) = -0.853 2, R(NMCA) = -0.745 4 and R(DCAN) = 0.369 7, respectively., Conclusion: Since NAR and NV coincide with the subjective perception of patients with nasal obstruction, they can be used as the sensitive parameters to evaluate subjective symptoms of patients.

Objective: To investigate the operative effect and value of window partial laryngectomy with endoscopy for treatment of stage T1b--T3 laryngeal cancer., Method: Twenty-seven cases with glottic laryngeal cancer were treated by window partial laryngectomy with endoscopy. After 3-year and 5-year survival rate and laryngeal functions (respiratory, pronunciation, swallowing function) recovery were evaluated., Result: The 3- and 5-year survival rates were 83.3% (15/18) and 75.0% (9/12) respectively. The decannulation rate was 92.6% (25/27) 4 weeks after operation. Three months after decannulation of respiratory function evaluation: the march to fast runner 77.8% (21/27), the jogger 14.8 (4/27), who walk briskly 7.4% (2/27). All patients had recovered after four weeks swallowing without choking cough and satisfied with phonation. Local recurrence rates at 3 and 5 year after operation were 10.5% (2/19) and 15.4% (2/13) respectively., Conclusion: The research shows that window partial laryngectomy with endoscopy was applicable to stage T1b--T2 and selecting T3 laryngeal cancer patients. Postoperative respiratory, pronunciation and swallowing function recovery rate is satisfactory.

Objective: To explore related issues of image-guidance system in oto-rhino-surgery application through 5 cases of ear and nose diseases., Method: All operations were carried out with endoscope or microscope under the guidance of computer aided landmark system. Five patients include one fungus sphenoid sinusitis, one enormous cyst of ethmoid-frontal sinus and three congenital external meatus block., Result: Preoperative preparation time is 16-30 minutes, with an average of 27 minutes. The quotient of calibration is 1.3-2.0, with an average of 1.92. Precise error between image and entity are less than 1 mm in base of skull, mastoid; less than 1.3 mm in nasal cavity and sinuses. Operations were successfully finished without complication intraoperatively or postoperatively. The time spent on surgery with image-guidance system is as similar as that of conventional way., Conclusion: Image-guidance system is useful for doctors to precisely recognize the mark of high dangerous area in nose, ear and surroundings, which is helpful to improve both the accusation and safety. It is one of the developing directions of microsurgery on otolaryngology field in the future.