Pyroptosis and its role in cancer

Programmed cell death(PCD)is mediated by specific genes that encode signals.It can balance cell survival and death.Pyroptosis is a type of inflammatory,caspase-dependent PCD mediated by gasdermin proteins,which function in pore formation,cell expansion,and plasma membrane rupture,followed by the release of intracellular contents.Pyroptosis is mediated by caspase-1/3/4/5/11 and is primarily divided into the classical pathway,which is dependent on caspase-1,and the non-classical pathway,which is dependent on caspase-4/5/11.Inflam-masomes play a vital role in these processes.The various components of the pyroptosis pathway are related to the occurrence,invasion,and metastasis of tumors.Research on pyroptosis has revealed new options for tumor treatment.This article summarizes the recent research progress on the molecular mechanism of pyroptosis,the relationship between the various components of the pyroptosis pathway and cancer,and the applications and prospects of pyroptosis in anticancer therapy.

Comparison of pain media and inflammatory factors after percutaneous transforaminal endoscopic discectomy and traditional fenestration operation treatment of protrusion of lumbar intervertebral disc

Objective:To compare the differences in pain mediators and inflammatory factors after percutaneous transforaminal endoscopic discectomy and traditional fenestration operation treatment of protrusion of lumbar intervertebral disc. Methods:80 patients with protrusion of lumbar intervertebral disc treated in our hospital between March 2013 and December 2015 were collected and divided into observation group and control group (n=40) according to randomized parallel contrast. Control group received traditional fenestration operation and observation group received percutaneous transforaminal endoscopic discectomy. Before operation and 1 week after operation, fluorescence spectrophotometry was used to determine serum pain medium levels;ELISA was used to determine pro-inflammatory factor and anti-inflammatory factor levels. Results:Before operation, differences in serum pain medium and inflammatory factor levels were not statistically significant between two groups (P>0.05). 1 week after operation, serum pain media norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), prostaglandin E2 (PGE2) and substance P (SP) levels as well as pro-inflammatory factors interleukin-1β(IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18) and tumor necrosis factor alpha (TNF-α) levels of observation group were lower than those of control group (P<0.05) while serum anti-inflammatory factors interleukin-4 (IL-4), interleukin 10 (IL-10), soluble tumor necrosis factor receptor I (sTNF-RI) levels were higher than those of control group (P<0.05). Conclusions:Percutaneous transforaminal endoscopic discectomy can effectively treat protrusion of lumbar intervertebral disc and is more advantageous in alleviating patients’ perception of pain and reducing inflammation.

Thyrotoxicosis after a massive levothyroxine ingestion: A case report

BACKGROUND The literature on thyrotoxicosis caused by excessive ingestion of exogenous thyroid hormone is limited,and most cases reported have involved pediatric clinical studies.CASE SUMMARY A 21-year-old woman initially presented with palpitation and chest tightness after an overdose of levothyroxine(10 mg).The patient transiently lost consciousness and developed atrial fibrillation during hospitalization.We used propylthiouracil to decrease the peripheral conversion of T4 to T3 and inhibit the synthesis of endogenous thyroxine,propranolol to control heart rate,hydrocortisone to correct severe thyrotoxicosis,and hemoperfusion to increase levothyroxine clearance.The patient recovered and was discharged.CONCLUSION For patients with thyrotoxicosis after taking excess levothyroxine,it is critical to monitor vital signs and initiate effective treatment.

Effect of acupuncture combined with transforaminal endoscopic therapy on pain mediators,neural function and stress response in patients with lumbar disc herniationn

Objective: To study the effect of acupuncture combined with transforaminal endoscopic therapy on pain mediators, neural function and stress response in patients with lumbar disc herniation. Methods: A total of 118 patients with lumbar disc herniation who were treated in the hospital between January 2015 and January 2017 were collected and divided into control group (n=59) and observation group (n=59) by random number table method. The control group received transforaminal endoscopic therapy, and the observation group received acupuncture combined with transforaminal endoscopic therapy. The differences in the pain mediators, neural function and stress response were compared between the two groups before and after treatment. Results: Before treatment, the differences in serum pain mediator contents, lower limb nerve conduction velocity and serum stress hormone contents were not statistically significant between the two groups. After treatment, serum PGE2, 5-HT, NO, Cor, INS and NE contents of both groups of patients were lower than those before treatment while serum β-EP contents as well as tibial nerve MCV, common peroneal nerve MCV, superficial peroneal nerve SCV and sural nerve SCV levels were higher than those before treatment, and serum PGE2, 5-HT, NO, Cor, INS and NE contents of observation group were lower than those of control group while serum β-EP content as well as tibial nerve MCV, common peroneal nerve MCV, superficial peroneal nerve SCV and sural nerve SCV levels was higher than those of control group. Conclusion: Acupuncture combined with transforaminal endoscopic therapy can effectively alleviate the pain, inhibit the stress response and optimize the neural function of lower limbs in patients with lumbar disc herniation.

scRNA-seq reveals that origin recognition complex subunit 6 regulates mouse spermatogonial cell proliferation and apoptosis via activation of Wnt/β-catenin signaling

The regulation of spermatogonial proliferation and apoptosis is of great significance for maintaining spermatogenesis.The single-cell RNA sequencing(scRNA-seq)analysis of the testis was performed to identify genes upregulated in spermatogonia.Using scRNAseq analysis,we identified the spermatogonia upregulated gene origin recognition complex subunit 6(Orc6),which is involved in DNA replication and cell cycle regulation;its protein expression in the human and mouse testis was detected by western blot and immunofluorescence.To explore the potential function of Orc6 in spermatogonia,the C18-4 cell line was transfected with control or Orc6 siRNA.Subsequently,5-ethynyl-2-deoxyuridine(EdU)and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays,flow cytometry,and western blot were used to evaluate its effects on proliferation and apoptosis.It was revealed that ORC6 could promote proliferation and inhibit apoptosis of C18-4 cells.Bulk RNA sequencing and bioinformatics analysis indicated that Orc6 was involved in the activation of wingless/integrated(Wnt)/β-catenin signaling.Western blot revealed that the expression ofβ-catenin protein and its phosphorylation(Ser675)were significantly decreased when silencing the expression of ORC6.Our findings indicated that Orc6 was upregulated in spermatogonia,whereby it regulated proliferation and apoptosis by activating Wnt/β-catenin signaling.

Difference in microstructural characteristics of stamp-charged coke and gravity-charged coke with approximate macroscopic performance

The microstructural characteristics including optical texture,porosity and pore structure and chemical structure of stamp-charged coke(SCC)and gravity-charged coke(GCC)with similar conventional macro-indicators were investigated,and the properties including micro-strength,reactivity of coke matrix and that after alkali enrichment were comparatively studied by various characterization methods.The anisotropic structure of SCC is composed of high content of fine mosaic texture,while the content of medium mosaic texture,coarse texture and fibrous texture is low.The statistical average shows that the fine mosaic average of SCC(24.89%)is 3.78 times the GCC average(6.58%),and the coarse mosaic average(1.24%)is only about 1/3 of the GCC average(3.43%).The porosity of SCC is lower than that of GCC,but tamping process does not lead to the fact that the number of closed pores of SCC is significantly lower than that of GCC.Although the structure of SCC is compact,its pore number is large and the pore wall is thin.Pores of coke with diameter less than 150 nm seem unaffected by tamping process.The aromatic structure of SCC was less ordered than that of GCC,which was speculated to be related to the addition of more low metamorphic coal in coking.The microscopic strength and structural strength of SCC are lower than those of GCC.The reactivity of coke matrix is affected by the specific surface area,but it is not the determining factor of its macro-reactivity.The improvement in dissolution reactivity of coke after potassium enrichment is independent of coke type.

Changes in the supply and demand potentials of China's glacier water resources in the 21st century:Spatiotemporal mismatches and combined effects

China's glacier water resources(GWRs)are not only indispensable suppliers of fresh water for humans living in large domestic areas but also affect the water supply to downstream neighbouring countries.Therefore,it is crucial to systematically evaluate the spatiotemporal(mis-)matches between the supply and demand potentials of China's GWRs and the combined supply and demand effects in the 21st century to enable regional sustainable development.To facilitate such research,in this study,we first regionalized the importance of China's GWRs in terms of the supply potential and downstream human dependence to reveal the spatial(mis-)matches between supply and demand potentials.Then,changes in the service potential of glacier meltwater and in population dynamics,as well as their temporal(mis-)matches and associated opportunities and risks,were further assessed at the river basin scale.The results showed that GWR plays an important role in 4 of 16 macroscale glacier-fed basins(i.e.,Tarim,Junggar,Ili,and Zangxi)and 11 of 37 subbasins within the China region due to higher supply potential and demand potential in those basins.The importance of China's GWRs increases dramatically when taking the demand potential of downstream countries into account,especially in the Ganges and Indus river basins.The peaks in meltwater runoff from the most glacierized basins of the eastern Tianshan Mountains,eastern Qilian Mountains,and southeastern Tibetan Plateau of China occur slightly earlier than the projected peak population(around 2030)under the mid-range Shared Socioeconomic Pathway(SSP245),leading to a compound risk in terms of decreasing meltwater supply and increasing human dependence at the end of the 2020s.However,the peak meltwater is expected to occur later than the peak population in the Tarim,Qiangtang Plateau,and Qaidam basins.The opportunities offered by the increase in meltwater can relieve the water resource pressure for those populations under water-stressed conditions.Greater attention should also be paid to water shortage risks in the transboundary river basins,especially in the Indus and Ganges basins,because the peak meltwater within China is generally expected to occur sooner than the projected peak population of downstream countries.This study provides an effective planning and decision-making basis for the full utilization of China's GWRs and adaptation when glacier runoff declines.

Effects of acupuncture in treating insomnia due to spleen-stomach disharmony syndrome and its influence on intestinal microbiome: Study protocol for a randomized controlled trial

Background: Insomnia is a common complaint that is closely related to gastrointestinal symptoms, which is consistent with the traditional Chinese medicine classical theory of ‘‘stomach disharmony leading to restless sleep." Acupuncture is an effective complementary and alternative medicine therapy to improve gastrointestinal function and restore the normal sleep-wake cycle. However, studies on the effectiveness of acupuncture for insomnia due to spleen-stomach disharmony syndrome are limited to case reports and few randomized controlled trials; deeper research on its mechanism is still lacking. This randomized controlled trial aims to assess the treatment efficacy of ‘‘harmonizing stomach to tranquilize mind"acupuncture for insomnia and its influence on the intestinal microbiome.Methods/design: This is a randomized, single-blind, parallel-group study. Sixty eligible patients with insomnia due to spleen-stomach disharmony syndrome will be randomly divided into two groups(1:1 allocation ratio). The intervention group will use ‘‘harmonizing stomach to tranquilize mind"acupuncture, and the control group will receive sham acupuncture. Participants will receive 5 acupuncture treatment sessions per week for 4 consecutive weeks. The Pittsburgh Sleep Quality Index will be used to evaluate the clinical efficacy of acupuncture treatment by making assessments at baseline, the end of treatment and the end of the follow-up. High-throughput 16 S ribosomal ribonucleic acid gene sequencing will be performed to detect changes in the intestinal microbial composition before and after treatment.Discussion: The results of this trial are expected to confirm that ‘‘harmonizing stomach to tranquilize mind" acupuncture can effectively relieve insomnia and alter the intestinal microbiome.

Exposure to herbicides reduces larval sensitivity to insecticides in Spodoptera litura (Lepidoptera: Noctuidae)

Herbicides and insecticides are widely used in modern agriculture. It has been reported in various studies that application of insecticides can increase tolerance of herbivorous insects to insecticides. However, limited information exists on susceptibility to insecticides when insects are exposed to herbicides. This study was conducted to investigate the potential impact of the herbicides trifluralin and 2-methyl-4-chlorophenoxyacetic acid sodium salt (MCPA-Na) on the susceptibility of the nocturnal moth Spodoptera litura to the insecticides X-cyhalothrin, phoxim and bifenthrin. We found that larvae exposed to trifluralin or MCPA-Na became significantly less susceptible to both insecticides than nonexposed control larvae. Herbicide-treated larvae did not show altered growth under the used test conditions. However, heads of herbicide-treated larvae showed increased expression of the acetylcholinesterase genes SI Ace I and SI Ace 2. Moreover, the fat body and midgut of herbicide-treated larvae displayed elevated expression of detoxification genes (the carboxylesterase gene SI CarE;the glutathione S-transferase genes SlGSTe2 and SlGSTe3\ the cytochrome P450 monooxygenase genes CYP6B48, CYP9A40 and CYP321B1). The CYP6B48 gene exhibited highest inducibility. In conclusion, the data of this study suggest that exposure of S. litura larvae to herbicides may stimulate detoxification mechanisms that compromise the efficacy of insecticides.

Effect of glaciers on the annual catchment water balance within Budyko framework

The effects of catchment characteristics and climate variables on water partitioning into evapotranspiratio n and runoff can be evaluated using the Budyko framework.However,the influence of glaciers on catchment characteristics within the framework has yet been adequately investigated.Here we extend the Budyko framework and apply the elasticity method to examine the effects of glaciers on runoff between 2001 and 2010 in 25 upstream catchments of the Tarim River Basin in western China.The consideration of glacier mass balance and glacier fraction improves the performance of the Budyko framework,especially for the catchments with a high glacier fraction.We found that the catchment characteristic parameterwas strongly affected by glacier fraction,and it changes from 1.15 to 2.09 when glacier fraction decreases from 0.4191 to 0.0005.This also reflects the change in water-energy partitioning that eventually effects on evapotranspiration and runoff.We further assessed the average runoff responses to changes in precipitation,potential evapotranspiration,glacier mass balance,and glacier fraction in the 25 catchments.Although the runoff appears most sensitive to precipitation in average,its sensitivity to glacier mass balance and glacier area in fact rises from-0.07%to 0.17% and about 0-0.54%,respectively,when the glacier fraction increases from 0.0005 to 0.4191,further demonstrating the increasing influence of glaciers when the fraction becomes larger.After all,the inclusion of glacier factors in the Budyko framework allows us to understand more about the impacts and contributions of glaciers to runoff at a catchment scale.