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Abstract High altitude is characterized by low oxygen, low pressure, and high radiation. When migrates from low to high altitudes, the body’s tissues and organs experience hypoxic stress and will present acoustic adaptation as the protective response. However, the mechanisms of acoustic adaptation at high altitudes remain unclear. In this study, cochlear tissues from Wistar rats were collected at 15, 30, 60, 120, and 180 days after high-altitude migration. Transcriptome sequencing was conducted and DESeq algorithm revealed expression patterns of Differentially Expressed Genes(DEGs) after high altitude migration. Day 60 is a critical stage for cochlear tissue “damage” and “repair” in high-altitude conditions. Transmission Electron Microscopy (TEM) observations of structures also support the findings. A time-series gene co-expression network algorithm was used to investigate gene regulatory patterns and key genes after migration. Immunofluorescence, immunohistochemistry, and qPCR were per-formed for key gene validation and localization. At Day 60, the peak DEG count occurs in rats migrating to high altitude, aligning with the critical phase for cochlear tissue damage and repair at high altitudes. Repair hinges on synaptic plasticity and myelination-linked processes, influencing modules M4 to M6. Module M4’s activation gradually diminishes from its peak. However, the ‘damage’ effect is orchestrated by inflammation-related processes in modules M3 to M5, with module M3’s activation also waning. Key gene module M4, pivotal for repair during this pivotal phase, encompasses Sptbn5, Cldn1, Gfra2, and Lims2 as its core genes. Immunohistochemistry reveals Sptbn5’s presence in cochlear neurons, hair cells, Schwann cells and stria vascularis tissue. Cldn1 and Gfra2 predominantly localize within the cochlear neuron region. These results may suggest new directions for future research on acoustic acclimatization to high altitude.

Plumbagin (PLB), a naphthoquinone compound, has been proven to have anti-cancer properties in different types of cancers. However, the anti-tumor actions as well as molecular processes in osteosarcoma (OS) remain unclear. This study investigates the underlying mechanisms of PLB in human OS cells in vitro. Our study showed that PLB significantly inhibited the proliferation of human OS cells in a time- and dosage-dependent manner. RNA sequencing data revealed that the efficacy of PLB is related to cell cycle, cell death, and p38 MAPK signaling pathway in KHOS-240S cells. Further studies indicated that PLB triggers G2/M phase arrest, mitochondrial-dependent apoptosis, as well as ferroptosis in human OS cells. Mechanistically, PLB treatment increased ROS generation that activates the p38 MAPK signaling pathway. BIRB 796, a p38 MAPK inhibitor, partly reversed PLB-induced phase arrest of G2/M and cell death. Furthermore, N-acetylcysteine (NAC), a ROS scavenger, significantly decreased G2/M phase arrest and cell death and reversed p38 MAPK activation caused by PLB. In conclusion, PLB induces arrest G2/M arrest, apoptosis as well as ferroptosis in human OS cells via ROS generation and p38 MAPK activation. There is potential for PLB to be an effective treatment for OS.

Highlights Donor–acceptor-linked covalent organic framework (COF)-based electrolyte can not only fulfill highly-selective Li+ conduction, but also offer a crucial opportunity to understand the role of electronic density in quasi-solid-state Li metal batteries. Donor–acceptor-linked COF electrolyte results in Li+ transference number 0.83, high ionic conductivity 6.7 × 10–4 S cm−1 and excellent cyclic ability in Li metal batteries. In situ characterizations, density functional theory calculation and time-of-flight secondary ion mass spectrometry are adopted to expound the mechanism of the rapid migration of Li+ in the “donor–acceptor” electrolyte system.

We employ the block negative dislocation model to invert the distribution of fault coupling and slip rate deficit on the different segments of the Tanlu (Tancheng-Lujiang) fault zone, according to the GPS horizontal velocity field from 1991 to 2007 (the first phase) and 2013 to 2018 (the second phase). By comparing the deformation characteristics results, we discuss the relationship between the deformation characteristics with the M earthquake in Japan. The results showed that the fault coupling rate of the northern section of Tancheng in the second phase reduced compared with that in the first phase. However, the results of the two phases showed that the northern section of Juxian still has a high coupling rate, a deep blocking depth, and a dextral compressive deficit, which is the enrapture section of the 1668 Tancheng earthquake. At the same time, the area strain results show that the strain rate of the central and eastern regions of the second phase is obviously enhanced compared with that of the first phase. The occurrence of the great earthquake in Japan has played a specific role in alleviating the strain accumulation in the middle and south sections of the Tanlu fault zone. The results of the maximum shear strain show that the shear strain in the middle section of the Tanlu fault zone in the second phase is weaker than that in the first phase, and the maximum shear strain in the southern section is stronger than that in the first phase. The fault coupling coefficient of the south Sihong to Jiashan section is high, and it is also the unruptured section of historical earthquakes. At the same time, small earthquakes in this area are not active and accumulate stress easily, so the future earthquake risk deserves attention.

Systemic amyloidosis is a rare protein misfolding and deposition disorder leading to progressive organ failure. Waldenström macroglobulinemia (WM) with systemic amyloidosis as the main manifestation is even rarer. The patient in this study presented with recurrent diarrhea and had not been diagnosed in other hospitals on multiple occasions. Later, his diarrhea worsened and was accompanied by sunken edema of both lower limbs and dizziness. Renal biopsy showed deposits of PAS light-staining material in the glomeruli, interstitium, and small arteries, which stained positively with Congo red. Cardiac ultrasound showed interventricular septum thickening of 17 mm, right ventricular wall myocardial thickening of approximately 0.6 cm, and septal thickening of approximately 0.5 cm, considering myocardial amyloidosis. Electromyography showed abnormal peripheral nerve conduction. Lymphoplasmacytic cells were found in the bone marrow. Taken together, he was diagnosed with WM. He was treated with a BR (Bendamustine + Rituximab) regimen. After 6 courses, the patient’s discomfort was relieved, his weight gained 5 kg, the level of serum IgM and dFLC decreased, and cardiac and renal assessments were more relieved. The patient has been followed up for more than 1 month.

In recent years, the "Room Escape" industry in China is booming, and this real live game has become popular. However, health threatening events such as fire, trauma, coma, and lung infection in the game venues have been reported at home and abroad. If these venues are not supervised in time, there will be great potential public safety and health hazards. In this review, we summarized the hidden dangers of public safety and health in such venues, including fire and safety hazards, persistent stress state, indoor ventilation problems, risk of contagious infection, non-player characters’ health risk, special film effects of 4D cinemas, mosquito problems, light pollution and noise, and food safety. Meanwhile, health management recommendations for the game venues were proposed from the aspects of formulating health management standards, improving health security measures, and strengthening related health education to players, so as to improve the hygiene levels of such venues and protect players and staff from injuries or diseases.

Giardia duodenalis is a zoonotic intestinal protozoan parasite that may cause host diarrhea and chronic gastroenteritis, resulting in great economic losses annually and representing a significant public health burden across the world. However, thus far, our knowledge on the pathogenesis of Giardia and the related host cell responses is still extensively limited. The aim of this study is to assess the role of endoplasmic reticulum (ER) stress in regulating G0/G1 cell cycle arrest and apoptosis during in vitro infection of intestinal epithelial cells (IECs) with Giardia. The results showed that the mRNA levels of ER chaperone proteins and ER-associated degradation genes were increased and the expression levels of the main unfolded protein response (UPR)-related proteins (GRP78, p-PERK, ATF4, CHOP, p-IRE1, XBP1s and ATF6) were increased upon Giardia exposure. In addition, cell cycle arrest was determined to be induced by UPR signaling pathways (IRE1, PERK and ATF6) through upregulation of p21 and p27 levels and promotion of E2F1-RB complex formation. Upregulation of p21 and p27 expression was shown to be related to Ufd1-Skp2 signaling. Therefore, the cell cycle arrest was induced by ER stress when infected with Giardia. Furthermore, the apoptosis of the host cell was also assessed after exposure to Giardia. The results indicated that apoptosis would be promoted by UPR signaling (PERK and ATF6), but would be suppressed by the hyperphosphorylation of AKT and hypophosphorylation of JNK that were modulated by IRE1 pathway. Taken together, both of the cell cycle arrest and apoptosis of IECs induced by Giardia exposure involved the activation of the UPR signaling. The findings of this study will deepen our understanding of the pathogenesis of Giardia and the associated regulatory network.

Dechlorane 602 (Dec 602) has biomagnification potential. Our previous studies suggested that exposure to Dec 602 for 7 days induced colonic inflammation even after 7 days of recovery. To shed some light on the underlying mechanisms, disturbances of gut immunity and gene expression were further studied. Adult C57BL/6 mice were administered orally with Dec 602 for 7 days, then allowed to recover for another 7 days. Colonic type 3 innate lymphoid cells (ILC3s) in lamina propria lymphocytes (LPLs) and lymphocytes in mesenteric lymph nodes (MLNs) were examined by flow cytometry. Expressions of genes in the gut were determined by RNA-Seq. It was found that Dec 602 exposure up-regulated the percentage of CD4+ T cells in MLNs. The mean fluorescent intensity (MFI) of interleukin (IL)− 22 in LPLs was decreased, while the MFI of IL-17a as well as the percentage of IL-17a+ ILC3s in LPLs were increased after exposure to Dec 602. Genes involved in the formation of blood vessels and epithelial-mesenchymal transition were up-regulated by Dec 602. Ingenuity pathway analysis of differentially expressed genes predicted that exposure to Dec 602 resulted in the activation of liver X receptor/retinoid X receptor (LXR/RXR) and suppression of muscle contractility. Our results, on one hand, verified that the toxic effects of Dec 602 on gut immunity could last for at least 14 days, and on the other hand, these results predicted other adverse effects of Dec 602, such as muscle dysfunction. Overall, our studies provided insights for the further investigation of Dec 602 and other emerging environmental pollutants.

In the electronics industry, graphene is applied with modified lead-free solder. This review presents advances in the preparation, strengthening mechanisms, and property characterization of graphene composite solders. Graphene composite solders are divided into two main categories: unmodified graphene and metal-particle-modified graphene. The unmodified graphene composite solders are classified according to the different solder systems. Metal-particle-modified graphene composite solders are classified according to different metal particles. However, there are still challenges with graphene composite solders. The main challenge is the poor bonding of graphene to the substrate and the nonuniform dispersion. Future directions for the development of graphene composite solders are proposed. They can provide some reference for the development of new graphene composite solders in the future.

Background: Chlorinated flame retardant Dechlorane 602 (Dec 602) has been detected in daily food, indicating that it may pose a risk to intestinal health. The intestinal microenvironment plays an important role in intestinal health. Intestinal microbiota and metabolites are two important factors for maintaining the microenvironment. However, little is known about the effects of Dec 602 on intestinal microbiota and metabolites. Objectives: We aimed to probe the effects of Dec 602 on the intestine by revealing the changes that Dec 602 caused to the intestinal microbiota and metabolites. Methods: Adult female C57BL/6 mice were exposed to Dec 602 (low/high doses: 1.0/10.0 μg/kg body weight per day) orally for 7 consecutive days, and sacrificed after 7 days of recovery. The composition of colonic microbiota was measured by 16S rRNA gene sequencing, and the colonic metabolites were determined by LC-ESI-MS/MS. Finally, the effects of Dec 602 on the colon were validated by histopathological analysis. Results: The intestinal microbiota composition was altered toward a pro-inflammatory status after exposure to Dec 602. Dec 602 exposure also up-regulated oxidative metabolites (glutathione disulfide, taurine and retinoic acid) and pro-inflammatory metabolites (prostaglandin E2). On the other hand, antioxidative metabolites (s-adenosylmethionine and 11-cis-retinol) and anti-inflammatory metabolites (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) were down-regulated after exposure to Dec 602. Infiltration of lymphocytes in the colonic lamina propria was observed in the mice treated with Dec 602 for 7 days, and it was not recovered after another 7 days without further treatment. Conclusion: Dec 602 interfered with the colonic microbiota and metabolome, and exhibited inflammatory features. Histopathological studies confirmed that Dec 602 exposure did induce colonic inflammation.

Background and objectives: China has experienced a serious public health burden because of the increased incidence of ischemic stroke. Evidence describing the association between short-term exposure to nitrogen dioxide (NO2) and ischemic stroke morbidity is limited, and few studies have focused on the effects of season and temperature. This study aimed to evaluate the acute effects of NO2 on ischemic stroke incidence in Shenzhen, a southeastern city of China, considering the modified effects of season and temperature. Methods: A time-stratified case–crossover study was conducted between 2003 and 2014 among 98,482 ischemic stroke hospitalizations. Conditional quasi-Poisson regression was used to estimate the percentage changes in ischemic stroke admissions in relation to each 10 μg/m3 increment in NO2. Results: NO2 was positively associated with ischemic stroke onset over the full year, as well as in the cold season (November through April) and on cold days (ambient temperature≤median temperature), with significant single-day effects within 3 days after the exposure, and significant cumulative effects within the delayed five days. The maximum percentage changes were obtained at lag0–5, with 1.81% (95% confidence interval (CI) was 0.86–2.76%) over the full year, 2.75% (1.48–4.03%) in the cold season, and 3.04% (1.74–4.35%) on cold days. Additionally, the effects of exposure were found to be greater in males and people with higher education, and were lasting longer in subgroups of older individuals. Conclusions: Our findings provide evidence that reductions in NO2 levels might decrease ischemic stroke morbidity, and enhance the understanding of ischemic stroke occurrence associated with NO2 modified by season and temperature.

The longitudinal distance between the vehicle and the forward vehicle, as well as the longitudinal distance between the vehicle and the opposite vehicle, is the main risk factor of overtaking behavior on two-way two-lane roads. Accurate measurement of these distances is the basis and key to automatic driving technology of two-way two-lane roads. In order to measure these longitudinal distances and improve the ranging accuracy, a vehicle distance measurement method of two-way two-lane roads based on monocular vision was proposed. Firstly, the vehicle detection model suitable for two-way two-lane roads was trained using YOLOv5s neural network. Secondly, aiming at the problem that the camera roll angle is not considered in the traditional geometric ranging method, the influence of the roll angle of the camera on ranging results using the traditional geometric ranging method was analyzed. In addition, the improved geometric ranging method considering the roll angle of the camera was proposed. Then, tests were conducted on a two-way two-lane road, and the results showed that the proposed method was effective. Compared with other methods, the improved geometric ranging method has higher ranging accuracy in this scene and can provide a reference for vision-based vehicle distance measurement in multi-lane scenes.

Background: Metal exposures have been reported to be related to the progress of metabolic syndrome (MetS), however, the currents results were still controversial, and the evidence about the effect of multi-metal exposure on MetS were limited. In this study, we intended to evaluate the relationships between metal mixture exposure and the prevalence of MetS in a mid-aged and older population of China. Methods: The plasma levels of 13 metals (aluminum, magnesium, calcium, iron, manganese, cobalt, copper, arsenic, zinc, selenium, cadmium, molybdenum and thallium) were detected by inductively coupled plasma mass spectrometry (ICP-MS) in 1277 adults recruited from the Eighth Affiliated Hospital of Sun Yat-Sen University (Shenzhen, China). Logistic regression, the adaptive least absolute shrinkage and selectionator operator (LASSO) penalized regression analysis and restricted cubic spline (RCS) analysis were used to explore the associations and dose-response relationships of plasma metals with MetS. To evaluate the cumulative effect of metals, the Bayesian Kernel Machine Regression (BKMR) model was applied. Results: The concentrations of magnesium and molybdenum were lower in the MetS group (p

A high premium has been put on researching the effects of cold spells because of their adverse influence on people's daily lives and health. The study aimed to find the most appropriate definition of the cold spell in Shenzhen and quantify the impact of cold spells on mortality. Based on the daily mortality data in Shenzhen from 2013 to 2017 and the meteorological and pollutant data from the same period, we quantified the effect of cold spells using eight different definitions in the framework of a distributed lag non-linear model with a quasi-Poisson distribution. In Shenzhen, low temperatures increase the risk of death more significantly than high temperatures (using the optimal temperature as the cut-off value). Comparing the quasi-Akaike information criterion value, attribution fraction (b-AF), and attribution number (b-AN) for all causes of deaths and non-accidental deaths, the optimal definition of the cold spell was defined as the threshold was 3rd percentile of the daily average temperature and duration for 3 or more consecutive days (all causes: b-AF = 2.31% [1.01–3.50%], b-AN = 650; non-accidental: b-AF = 1.92% [0.57–3.17%], b-AN = 471). For cardiovascular deaths, the best definition was the temperature threshold as the 3rd percentile of the daily average temperature with a duration of 4 consecutive days (cardiovascular: b-AF = 1.37% [0.05–2.51%], b-AN = 142). Based on the best definition in the model, mortality risk increased in cold spells, with a statistically significant lag effect occurring as early as the 4th day and the effect of a single day lasting for 6 days. The maximum cumulative effect occurred on the 14th day (all-cause: RR = 1.54 [95% CI, 1.20–1.98]; non-accidental: RR = 1.43 [95% CI, 1.11–1.84]; cardiovascular: RR = 1.58 [95% CI, 1.00–2.48]). The elderly and females were more susceptible to cold spells. Cold spells and their definitions were associated with an increased risk of death. The findings of this research provide information for establishing an early warning system, developing preventive measures, and protecting susceptible populations.

High leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) expression caused by an inflammatory condition was reported to promote tumor proliferation and the epithelial-mesenchymal transition (EMT) in various malignant tumors, but those effects have not been studied in hypopharyngeal squamous cell carcinoma (HSCC) and the molecular mechanism remains unclear. This study was aimed to determine whether YAP/TAZ is involved in the regulation of LGR5 expression in the inflammatory condition. Human hypopharyngeal carcinoma FaDu cells were stimulated with inflammatory medium. The cell invasion ability were evaluated through wound healing assay and transwell invasion assay. The expression levels of EMT-related proteins, LGR5, and p-YAP were detected by real time PCR, western blotting, and immunofluorescence. The results showed that LGR5 expression and the EMT process were significantly enhanced under inflammatory condition. The expression of EMT-related proteins was up-regulated, while that of p-YAP was decreased. After inhibiting the high LGR5 expression with short interfering RNA, the expression of EMT-related proteins was also down-regulated, while that of p-YAP was significantly increased. The use of verteporfin (VP), an inhibitor of YAP activity that promotes YAP phosphorylation, did not affect LGR5 expression. In conclusion, we suggest that the inflammatory condition leads to high LGR5 expression, which up-regulating the expression of EMT-related proteins by inhibiting the YAP phosphorylation.

Objectives: This study aimed to investigate the associations between air pollution exposure and pediatric outpatient visits for dry eye disease (DED) in Shenzhen, China.Methods: Generalized additive models were utilized to explore the acute effects of air pollution exposure on pediatric outpatient visits for DED.Results: Single-day lag exposures to NO2, O3, PM2.5, and PM10 were associated with DED outpatient visits at lag days 0, 6, 4 and 2. Relative risks (RRs) for DED given a 10-μg/m3 increase in NO2, O3, PM2.5, and PM10 concentrations were 1.062[95% confidence interval (CI) 1.003, 1.123], 1.015(95% CI 1.001, 1.031), 1.052(95% CI 1.001, 1.115), and 1.038 (95% CI 1.002, 1.076), respectively. RR for DED given a 10-μg/m3 increase in NO2 over cumulative lag days 0–1 was 1.075 (95% CI 1.009, 1.147), and RR for DED given a 10-μg/m3 increase in PM10 over cumulative lag days 0–4 was 1.051 (95% CI 1.003, 1.102).Conclusion: The observed associations between air pollution and outpatient visits for DED may provide evidence for policy makers to consider implementing measures to reduce the risk of DED owing to air pollution in China.

Pepsin plays an important role in laryngopharyngeal reflux (LPR), a risk factor for the development of hypopharyngeal squamous cell carcinomas (HPSCC). However, the role of pepsin in HPSCC is not clear. We show by immunohistochemistry that pepsin positivity occurs in a significant proportion of human primary HPSCC specimens, and in many cases matched adjacent uninvolved epithelia are negative for pepsin. Pepsin positivity is associated with nodal involvement, suggesting that pepsin may have a role in metastasis. Treatment of FaDu cancer cells with pepsin increased cell proliferation, possibly by inducing G1/S transition. We also observed significant changes in expression of genes involved in NF-kappaB, TRAIL and Notch signaling. Our data suggest that pepsin plays an important role in HPSCC and that targeting pepsin could have potential therapeutic benefits.

Human adults are faster to respond to small/large numerals with their left/right hand when they judge the parity of numerals, which is known as the SNARC (spatial-numerical association of response codes) effect. It has been proposed that the size of the SNARC effect depends on response latencies. The current study introduced a perceptual orientation task, where participants were asked to judge the orientation of a digit or a frame surrounding the digit. The present study first confirmed the SNARC effect with native Chinese speakers (Experiment 1) using a parity task, and then examined whether the emergence and size of the SNARC effect depended on the response latencies (Experiments 2, 3, and 4) using a perceptual orientation judgment task. Our results suggested that (a) the automatic processing of response-related numerical-spatial information occurred with Chinese-speaking participants in the parity task; (b) the SNARC effect was also found when the task did not require semantic access; and (c) the size of the effect depended on the processing speed of the task-relevant dimension. Finally, we proposed an underlying mechanism to explain the SNARC effect in the perceptual orientation judgment task.