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Abstract Endoplasmic reticulum stress (ERS) is a cellular stress response characterized by excessive contraction of the endoplasmic reticulum (ER). It is a pathological hallmark of many diseases, such as diabetes, obesity, and neurodegenerative diseases. In the unique growth characteristic and varied microenvironment of cancer, high levels of stress are necessary to maintain the rapid proliferation and metastasis of tumor cells. This process is closely related to ERS, which enhances the ability of tumor cells to adapt to unfavorable environments and promotes the malignant progression of cancer. In this paper, we review the roles and mechanisms of ERS in tumor cell proliferation, apoptosis, metastasis, angiogenesis, drug resistance, cellular metabolism, and immune response. We found that ERS can modulate tumor progression via the unfolded protein response (UPR) signaling of IRE1, PERK, and ATF6. Targeting the ERS may be a new strategy to attenuate the protective effects of ERS on cancer. This manuscript explores the potential of ERS-targeted therapies, detailing the mechanisms through which ERS influences cancer progression and highlighting experimental and clinical evidence supporting these strategies. Through this review, we aim to deepen our understanding of the role of ER stress in cancer development and provide new insights for cancer therapy.

Abstract Background Colorectal cancer (CRC) is the second most common malignant tumor worldwide, and its incidence rate increases annually. Early diagnosis and treatment are crucial for improving the prognosis of patients with colorectal cancer. Circular RNAs are noncoding RNAs with a closed-loop structure that play a significant role in tumor development. However, the role of circular RNAs in CRC is poorly understood. Methods The circular RNA hsa_circ_0000467 was screened in CRC circRNA microarrays using a bioinformatics analysis, and the expression of hsa_circ_0000467 in CRC tissues was determined by in situ hybridization. The associations between the expression level of hsa_circ_0000467 and the clinical characteristics of CRC patients were evaluated. Then, the role of hsa_circ_0000467 in CRC growth and metastasis was assessed by CCK8 assay, EdU assay, plate colony formation assay, wound healing assay, and Transwell assay in vitro and in a mouse model of CRC in vivo. Proteomic analysis and western blotting were performed to investigate the effect of hsa_circ_0000467 on c-Myc signaling. Polysome profiling, RT‒qPCR and dual-luciferase reporter assays were performed to determine the effect of hsa_circ_0000467 on c-Myc translation. RNA pull-down, RNA immunoprecipitation (RIP) and immunofluorescence staining were performed to assess the effect of hsa_circ_0000467 on eIF4A3 distribution. Results In this study, we found that the circular RNA hsa_circ_0000467 is highly expressed in colorectal cancer and is significantly correlated with poor prognosis in CRC patients. In vitro and in vivo experiments revealed that hsa_circ_0000467 promotes the growth and metastasis of colorectal cancer cells. Mechanistically, hsa_circ_0000467 binds eIF4A3 to suppress its nuclear translocation. In addition, it can also act as a scaffold molecule that binds eIF4A3 and c-Myc mRNA to form complexes in the cytoplasm, thereby promoting the translation of c-Myc. In turn, c-Myc upregulates its downstream targets, including the cell cycle-related factors cyclin D2 and CDK4 and the tight junction-related factor ZEB1, and downregulates E-cadherin, which ultimately promotes the growth and metastasis of CRC. Conclusions Our findings revealed that hsa_circRNA_0000467 plays a role in the progression of CRC by promoting eIF4A3-mediated c-Myc translation. This study provides a theoretical basis and molecular target for the diagnosis and treatment of CRC.

Abstract Hepatocellular carcinoma (HCC) represents a major global health threat with diverse and complex pathogenesis. Aldo–keto reductase family 1 member B10 (AKR1B10), a tumor-associated enzyme, exhibits abnormal expression in various cancers. However, a comprehensive understanding of AKR1B10's role in HCC is lacking. This study aims to explore the expression characteristics of AKR1B10 in HCC and its correlation with clinicopathological features, survival prognosis, and tumor immune microenvironment, further investigating its role and potential regulatory mechanisms in HCC. This study conducted comprehensive analyses using various bioinformatics tools and databases. Initially, differentially expressed genes related to HCC were identified from the GEO database, and the expression of AKR1B10 in HCC and other cancers was compared using TIMER and GEPIA databases, with validation of its specificity in HCC tissue samples using the HPA database. Furthermore, the relationship of AKR1B10 expression with clinicopathological features (age, gender, tumor size, staging, etc.) of HCC patients was analyzed using the TCGA database's LIHC dataset. The impact of AKR1B10 expression levels on patient prognosis was evaluated using Kaplan–Meier survival analysis and the Cox proportional hazards model. Additionally, the correlation of AKR1B10 expression with tumor biology-related signaling pathways and tumor immune microenvironment was studied using databases like GSEA, Targetscan, and others, identifying microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate AKR1B10 expression to explore potential regulatory mechanisms. Elevated AKR1B10 expression was significantly associated with gender, primary tumor size, and fibrosis stage in HCC tissues. High AKR1B10 expression indicated poor prognosis and served as an independent predictor for patient outcomes. Detailed mechanism analysis revealed a positive correlation between high AKR1B10 expression, immune cell infiltration, and pro-inflammatory cytokines, suggesting a potential DANCR-miR-216a-5p-AKR1B10 axis regulating the tumor microenvironment and impacting HCC development and prognosis. The heightened expression of AKR1B10 in HCC is not only related to significant clinical-pathological traits but may also influence HCC progression and prognosis by activating key signaling pathways and altering the tumor immune microenvironment. These findings provide new insights into the role of AKR1B10 in HCC pathogenesis and highlight its potential as a biomarker and therapeutic target.

Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of Paeonia lactiflora Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2 % dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2 % DSS-induced Rag1−/− mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (Interleukin-17A, Granulocyte-macrophage colony stimulating factor, and Interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Abstract Cellular metabolism is the fundamental process by which cells maintain growth and self‐renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron‐dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron‐induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.

Abstract Several studies have reported the effects of DJ-1 gene and miR-199a/b-3p on HCC development. However, whether miR-199a/b-3p regulates HCC progression through a novel compensatory signaling pathway involving DJ-1, Ras, and PI3K/AKT remains unknown. We used (TCGA, HPA, miRWalk and Target scan) databases, cancer and para-tissue HCC patients, dual-luciferase reporter gene analysis, proteomic imprinting, qPCR, cell proliferation, scratch, transport, and flow cytometry to detect the molecular mechanism of DJ-1 and miR-199a/b-3p co-expression in HCC cell lines. Bioinformatics analysis showed that DJ-1 was highly expressed in HCC ((P

BackgroundInfant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum. However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum. Our goal was to reveal the differences in the intestinal microbiota of botulism-infected and healthy infants as well as the dynamic changes over time through multi-omics analysis.MethodsWe performed 16S rRNA sequencing of 20 infants’ stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants’ intestinal microbiota as well as function over time series.ResultsWe found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0C. botulinum isolates from the patients were typed into ST31 and ST32.ConclusionDifferences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants.

Background: This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. Methods: From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups’ progression-free survival and overall survival were also calculated to assess the treatment effect. Results: Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant ( P > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group ( P

BackgroundTraditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV.MethodsWe retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens.ResultsThis study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P

Ratoon rice, the production of second crop from the dormant buds on the stubble after harvesting of the main crop, is considered an economic, environment-sound, and resource-efficient cropping system. This paper summarized the research progress of ratoon rice in Chongqing Municipality, the upper reaches of the Yangtze River, China in the past 30 years, and analyzed the physiological mechanisms behind the rice varieties with strong ratooning ability and the key practices for achieving high yield of ratoon rice. Ratooning ability and grain yield of the ratoon crop are highly and positively correlated with the initiation and growth of axillary buds, which can be promoted by optimizing variety selection, nutrient and water management, crop establishment method, stubble height, and harvesting method of the main crop. With implementation of those key practices, the grain yield could reach as high as 7.2 ​t ​ha−1 of the ratoon crop with the main crop harvested manually. Due to the shortage of rural labor, mechanical harvesting of the main crop becomes an inevitable option for the sustainable development of ratoon rice. In the future studies, there is need to develop specialized harvesting machines and crop management strategies for reducing the rolling damage to stubbles during mechanical harvesting of the main crop, and consequently achieving high and stable yield of mechanized ratoon rice.

Abstract Soil bacterial communities regulate nutrient cycling and plant growth in forests. Although these bacterial communities vary with soil nutrients and plant traits, the variation and degree with soil horizons in different forest types remain unclear. Here, bacterial communities of 44 soil samples from organic horizon (O horizon) and mineral horizon (M horizon) of three forest types (Cunninghamia, broad-leaved and Pinus forests) in subtropical forests of Dabie Mountain, China were analyzed based on amplicon sequencing. We assessed the effects of soil horizons and forest types on bacterial communities. The results showed that the bacterial richness and diversity were significantly higher in the O horizon than in the M horizon. Furthermore, the bacterial community composition and functions were also remarkably different between the two soil horizons. Furthermore, forest types could affect bacterial community composition but not for diversity and functions. Moreover, soil organic matter, including the total organic carbon, available phosphorus, total organic nitrogen, available potassium, ammonium nitrogen, and pH were main drivers for bacterial community composition. The results propose robust evidence that soil horizons strongly driven bacterial community composition and diversity, and suggest that microhabitat of soil bacterial communities is important to maintain the stability of forest ecosystem.

Abstract Background Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by postpartum haemorrhage (PPH). Case Two women diagnosed as preeclampsia and hypofibrinogenemia developed severe PPH after undergoing Cesarean sections. Besides supplement with fibrinogen concentrate and supportive treatment, the second patient got administration of heparin after delivery and bleeding was stopped. The haemorrhage in case 1 didn’t disappear until an hysterectomy. The two patients both recovered and were discharged soon. Conclusions Severe preeclampsia patients with hypofibrinogenemia could suffer PPH. It’s necessary to detect and master coagulation function. Heparin could be considered to balance hypercoagulation and hypocoagulation to avoid catastrophic haemorrhage and hysterectomy.

This work used headspace solid-phase microextraction with gas chromatography–mass spectrometry (HS-SPME-GC–MS) to analyze the volatile components of hydrosols of Citrus × aurantium ‘Daidai’ and Citrus × aurantium L. dried buds (CAVAs and CADBs) by immersion and ultrasound–microwave synergistic-assisted steam distillation. The results show that a total of 106 volatiles were detected in hydrosols, mainly alcohols, alkenes, and esters, and the high content components of hydrosols were linalool, α-terpineol, and trans-geraniol. In terms of variety, the total and unique components of CAVA hydrosols were much higher than those of CADB hydrosols; the relative contents of 13 components of CAVA hydrosols were greater than those of CADB hydrosols, with geranyl acetate up to 15-fold; all hydrosols had a citrus, floral, and woody aroma. From the pretreatment, more volatile components were retained in the immersion; the relative contents of linalool and α-terpineol were increased by the ultrasound–microwave procedure; and the ultrasound–microwave procedure was favorable for the stimulation of the aroma of CAVA hydrosols, but it diminished the aroma of the CADB hydrosols. This study provides theoretical support for in-depth exploration based on the medicine food homology properties of CAVA and for improving the utilization rate of waste resources.

The Jimsar Sag is an important shale oil exploration target area in the Junggar Basin, northwestern China. The Permian Lucaogou Formation, with a thickness of 200–300 m, is the primary exploration target. High-frequency variation in lithology is a typical feature of the Lucaogou Formation, reflecting the fluctuation of the depositional environment and organic matter enrichment. The evolution of the depositional environment and accumulation mechanism of organic matter still need to be elucidated for the Lucaogou Formation. High-resolution sampling of the entire Lucaogou Formation was applied to a 248 m long core from Well JX in the Jimsar Sag to examine the depositional environment and organic matter enrichment. The findings unveiled that the Lucaogou Formation was deposited under a hot and arid climate, within the confines of a closed saline paleo-lake, where sediments endured an extended period of anoxic conditions, displayed periodic oscillations in paleo-temperature and paleo-salinity values over time, alongside a continuous rise in paleo-water depth. The predominant source lithology of the Lucaogou Formation is felsic igneous rock. Small-scale transgression and hydrothermal sedimentation occurred during the deposition of the Lucaogou Formation. The prevailing hot climate and enduring reducing environment fostered ideal circumstances for the enrichment of organic matter in the Lucaogou Formation. Due to different sedimentary environments and enrichment mechanisms, organic matter is enriched in two modes in the Lucaogou Formation.

It is well known that the existing horizontal-well-drilling and hydraulic fracturing technology used to achieve large-scale, cost-effective production from immature to low–moderate-maturity continental shale in China, where the organic matter mainly exists in solid form, is fairly ineffective. To overcome the obstacles, in situ conversion technology seems feasible, while implementing it in the target layer along with estimating the amount of expected recoverable hydrocarbon in such shale formations seems difficult. This is because there are no guidelines for choosing the most appropriate method and selecting relevant key parameters for this purpose. Hence, based on thermal simulation experiments during the in situ conversion of crude oil from the Triassic Chang 73 Formation in the Ordos Basin and the Cretaceous Nenjiang Formation in the Songliao Basin, this deficiency in knowledge was addressed. First, relationships between the in situ-converted total organic carbon (TOC) content and the vitrinite reflectance (Ro) of the shales and between the residual oil volume and the hydrocarbon yield were established. Second, the yields of residual oil and in situ-converted hydrocarbon were measured, revealing their sensitivity to fluid pressure and crude oil density. In addition, a model was proposed to estimate the amount of in situ-converted hydrocarbon based on TOC, hydrocarbon generation potential, Ro, residual oil volume, fluid pressure, and crude oil density. Finally, a method was established to determine key parameters of the final hydrocarbon yield from immature to low–moderate-maturity organic material during in situ conversion in shales. Following the procedure outlined in this paper, the estimated recoverable in situ-converted oil in the shales of the Nenjiang Formation in the Songliao Basin was estimated to be approximately 292 × 108 tons, along with 18.5 × 1012 cubic meters of natural gas, in an area of approximately 8 × 104 square kilometers. Collectively, the method developed in this study is independent of the organic matter type and other geological and/or petrophysical properties of the formation and can be applied to other areas globally where there are no available in situ conversion thermal simulation experimental data.

BackgroundFunctional dyspepsia (FD) refers to a group of clinical symptoms caused by gastric and duodenal dysfunction. Which is a chronic functional disorder of the gastrointestinal tract with no cure. Zhishixiaopi decoction (ZSXP) is a type of Chinese herbal prescription that for treating FD. Although some randomized controlled trials (RCTs) report that ZSXP can significantly improve FD clinical symptoms and/or laboratory results, the trial design varies greatly among studies, making it challenging to draw a conclusion of the efficacy of ZSXP in treating FD.DesignA systematic review and a meta-analysis.SettingMianyang Central Hospital.ObjectiveWe conducted a systematic review and a meta-analysis to evaluate the efficacy and safety of ZSXP for treating FD.MethodsWe developed inclusion and exclusion criteria based on FD diagnosed criteria, interventions to treat FD, and outcomes of these interventions. Search strategies combined disease terms, symptom terms, anatomy terms and intervention terms. Literature search was conducted on eight online databases in English or Chinese, including Medline (via PubMed), Embase (via Ovid), The Cochrane Library, Web of Science, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database.InterventionThe experimental group received oral administration of ZSXP and had a complete treatment process. ZSXP needs to fully contain the key herbal ingredients, regardless of whether the dosage of each herb is consistent with the original prescription. The Control group received monotherapy or combination therapy of other Western medicine and had a complete treatment process.OutcomesThe primary outcomes appraised were Total effective rate (TER), serum levels of Motilin(MOT), Gastrin(GAS) and Somatostatin (SS), Gastric emptying rate (GER) using a Barium meal method (GER(B)) and Gastric half emptying time using an Ultrasonic method (GHET(T1/2)). The Cochrane Bias Risk Tool was used for quality critical appraisal, Review Manager (RevMan) version 5.3 was used for statistical analysis.ResultsA total of 21 medium-quality RCTs were included in the meta-analysis. All 21 included studies were conducted and completed in Mainland China from 1998 to 2020. The treatment duration was between two weeks to two months. The meta-analysis suggests that, compared with the Western medicine treatment group, ZSXP treatment was more effective to improving the TER in FD [Odds ratio, OR = 3.54, 95%CI:(2.49, 5.05), Z = 6.99, PConclusionsThe meta-analysis suggests that Zhishixiaopi treatment is a relatively effective and safe traditional Chinese medicine prescription and could be used for functional dyspepsia treatment. Considering the limitations of this study, the conclusion needs to be further confirmed by high-quality, multi-center, and large-sample randomized controlled trials.

Liver cancer is a huge global challenge. It has been exacerbated by tumor-associated dendritic cells (TDCs) due to Endoplasmic Reticulum (ER) stress. We planned to investigate the effects of LBP3 on TDCs immune function, and to explore whether the underlying mechanism was associated with IRE1α-XBP1 pathway of ER stress regulating lipid metabolism. In our early studies, LBP3 (40–350 kDa) with significant anti-tumor and immunomodulatory activities was isolated from the polysaccharide of Lycium barbarum L. (LBP). Here, we determined that LBP3 had a great anti-tumor efficacy in H22-tumor bearing mice by functional activation of TDCs. In vivo and in vitro results showed that LBP3 could up-regulate the expression of MHC Ⅱ, CD80 and CD86 on TDCs, increase the level of TNF-α secreted by TDCs, enhance TDCs’ ability to improve the proliferation and immunosuppression of lymphocytes. Furthermore, LBP3 could decrease the high expression of ER stress-related proteins IRE1α, GRP78, XBP1 and CHOP, reduce the lipid accumulation, raise the low expression of costimulatory molecules on TDCs induced by thapsigargin (TG). Taken together, LBP3 could reduce intracellular lipid accumulation by inhibiting IRE1α-XBP1 pathway of ER stress, improve the function of TDCs to stimulate T cells, thence play an anti-tumor role.

Background: The sustainability and generalizability of China’s dynamic zero-COVID strategy on eliminating SARS-CoV-2 transmission has casted doubt globally, mainly because it has exacted high social and economic cost. This study aimed to estimate the disease burden during the first wave of Omicron in China and compared the cost-effectiveness of implementing a Real-world strategy (adjusted dynamic zero-COVID strategy) with two simulated strategies (routine and stricter dynamic zero-COVID strategy) to inform appropriate strategies for COVID-19 pandemic control. Methods: A dynamic state-transition simulation model was developed to compare the health and cost outcomes between different dynamic zero-COVID strategies. Omicron-related healthcare costs were estimated from the societal perspective. Epidemiological parameter values were derived from data of real-world or generated by model calibration; costs and effectiveness parameter values were informed either by local data or published literature. The primary outcomes were total social cost, disability adjusted life-years (DALYs) and net monetary benefit (NMB). Deterministic sensitivity analyses (DSA) and scenario analyses were performed to assess the model robustness. Results: The first wave of Omicron in Shanghai resulted in 47,646 DALYs lost and 415 billion RMB losses. At a willingness-to-pay threshold of 173,630 RMB (the GDP per capita of Shanghai in 2021) per DALY saved, the Real-world strategy was considered as the most cost-effective strategy due to its highest NMB (−407 billion). Results from DSA confirmed the robustness of our findings. Conclusion: Our finding supported the Real-world strategy taken by the Shanghai Municipal Government between March 1 and May 21, 2022 to control the first wave of Omicron outbreak. Moreover, our results indicated that whether the Stricter dynamic zero-COVID strategy is worth implementing at the beginning of the COVID-19 outbreak mainly depended on the infection rate of COVID-19 among primary contacts. Our analysis provides important evidence to inform policy makers to make appropriate decisions regarding COVID-19 pandemic management.

Aeromonas schubertii is a pathogen that severely affects aquatic animals, including the snakehead, Channa maculata. Lytic bacteriophages have been recognized as effective alternatives to antibiotics for controlling bacterial infections. However, there have been no reports of A. schubertii phages as far as we know. In this study, a lytic bacteriophage SD04, which could effectively infect A. schubertii, was isolated from pond water cultured with diseased snakehead. The SD04 phage formed small, round plaques on Petri dishes. Electron microscopy revealed a hexagonal head and a contractile tail. Based on its morphology, it may belong to the Myoviridae family. Two major protein bands with molecular weights of 50 and 38 kilodaltons were observed after the phage was subjected to SDS-PAGE. The phage showed a large average burst size, high specificity, and a broad host range. When stored at 4 °C, phage SD04 had high stability over 12 months and showed almost no variation within the first six months. All fish were healthy after both intraperitoneal injection and immersion administration of SD04, indicating the safety of the phage. After treatment with SD04, Channa maculata in both phage therapy groups and prevention groups showed high survival rates (i.e., 83.3 ± 3.3% and 100 ± 1.3%, respectively). Phage therapy inhibits bacterial growth in the liver, the target organ of the infected Channa maculat. The experimental results indicate the potential use of phage SD04 for preventing A. schubertii infection in Channa maculata.

Abstract Background Vitamin E is an essential nutrient in human body famous for its antioxidant and non-antioxidant functions. However, little is known about vitamin E deficiency status in urban adults of Wuhan from central China. Our aim is to describe the distribution of both circulating and lipid-adjusted serum vitamin E concentration in urban adults of Wuhan. Methods We hypothesized that the prevalence rate of vitamin E deficiency would be low in Wuhan in consideration of the Chinese food composition. A cross-sectional study with 846 adults was performed in a single-center. Concentrations of vitamin E were measured by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). Results The median (interquartile range, IQR) of serum vitamin E concentration was 27.40 (22.89–33.20) μmol/L while that of serum vitamin E concentration adjusted by total cholesterol or the sum of cholesterol (TC) and triglyceride (TG) (the sum of cholesterol and triglyceride, TLs) were 6.20 (5.30–7.48) and 4.86 (4.10–5.65) mmol/mol, respectively. No significant difference of the circulating and TC-adjusted vitamin E concentration was found between male and female except for vitamin E/TLs. However, concentrations of vitamin E increased significantly (r = 0.137, P

Abstract Background The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. Methods 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. Results The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74–0.83),0.85(95%CI 0.80–0.89),5.4(95%CI 3.8–7.5), 0.25(95%CI 0.20–0.31), 22(95%CI 13–35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64–0.81),0.70(95%CI 0.49–0.85),2.40(95%CI 1.3–4.7),0.38(95%CI 0.23–0.61),6(95%CI 2–19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. Conclusion The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.

IntroductionListeria monocytogenes is a globally distributed bacterium that exhibits genetic diversity and trait heterogeneity. The alternative sigma factor SigB serves as a crucial transcriptional regulator essential for responding to environmental stress conditions and facilitating host infection.MethodWe employed a comprehensive genetic analysis of sigB in a dataset comprising 46,921 L. monocytogenes genomes. The functional attributes of SigB were evaluated by phenotypic experiments.ResultsOur study revealed the presence of two predominant SigB factors (SigBT1 and SigBT2) in L. monocytogenes, with a robust correlation between SigBT1 and lineages I and III, as well as SigBT2 and lineage II. Furthermore, SigBT1 exhibits superior performance in promoting cellular invasion, cytotoxicity and enhancing biofilm formation and cold tolerance abilities under minimally defined media conditions compared to SigBT2.DiscussionThe functional characteristics of SigBT1 suggest a potential association with the epidemiology of lineages I and III strains in both human hosts and the natural environment. Our findings highlight the important role of distinct SigB factors in influencing the biological traits of L. monocytogenes of different lineages, thus highlighting its distinct pathogenic and adaptive attributes.

Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to play roles in various diseases, yet there is little data on their changes in patients with non-small-cell lung cancer (NSCLC). A simple LC-MS/MS method for EPA and DHA determination is critical to exploring EPA and DHA level changes in NSCLC patients. Methods: 25 µL of serum was mixed with 25 µL of internal standard working solution, and then 450 µL of acetonitrile for protein precipitation. After vortex and centrifugation, the supernatant was directly used for LC-MS/MS analysis. The method was well validated with linearity, precision, recovery, and matrix effect. The concentrations of EPA and DHA in serum samples from 211 NSCLC patients and 227 healthy controls were determined by this LC-MS/MS method. Results: Good separation and reliable quantification of EPA and DHA in serum samples were achieved by our method. Compared with healthy controls, serum EPA and DHA were significantly reduced in both adenocarcinoma and squamous cell carcinoma patients. The concentrations of EPA and DHA showed a progressive decrease in healthy controls, early- and advanced-stage NSCLC patients. Conclusions: This study identified significant reductions in serum EPA and DHA in NSCLC patients through the development of an LC-MS/MS method.

Context Chinese herb Huangqin decoction (HQD) can regulate intestinal flora in ulcerative colitis (UC) mice. Objective Our study clarifies the mechanism of HQD in regulating the intestinal flora of UC mice. Materials and methods Male C57BL/6 mice were randomly divided into six groups: Control, Model (3% DSS), Sulfasalazine (500 mg/kg), HQD-L (250 mg/kg), HQD-M (500 mg/kg), and HQD-H (1000 mg/kg) groups. Measurement of body weight, colon length, DAI, and haematoxylin–eosin staining were conducted. FISH and 16S rDNA detected colonic bacterial infiltration and intestinal flora changes. The expression of RegIIIγ and PRRs (NOD2, TLR5, TLR4) were detected by FCM and WB, respectively. In addition, WB, qPCR, or IHC were used to detect the expression of NOD2, MyD88, RIP2, and NF-κB p65 in the colon. ELISA was used to determine cytokines. Results Compared with the model group (DAI score, 2.38 ± 0.05; histological score, 4.08 ± 0.54), HQD treatment significantly reduced the DAI score (L, 2.16 ± 0.09; M, 1.45 ± 0.05; H, 1.18 ± 0.05) and histological score (L, 3.16 ± 0.82; M, 2.50 ± 0.81; H, 1.51 ± 0.76); restored the weight, the colonic length (p

Listeria monocytogenes (L. monocytogenes) is a pathogen that is transmitted through contaminated food and causes the illness known as listeriosis. The virulence factor InlA plays a crucial role in the invasion of L. monocytogenes into the human intestinal epithelium. In addition, InlA enhances the pathogenicity of host strains, and different strains of L. monocytogenes contain varying variations of InlA. Our study analyzed a total of 4393 published L. monocytogenes genomes from 511 sequence types (STs) of diverse origins. We identified 300 unique InlA protein sequence types (PSTs) and revealed 45 highly mutated amino acid sites. The leucine-rich repeat (LRR) region was found to be the most conserved among the InlA, while the protein A (PA) region experienced the highest mutation rate. Two new types of mutations were identified in the B-repeat region of InlA. Correspondence analysis (CA) was used to analyze correlations between the lineages or 10 most common sequence types (STs) and amino acid (aa) sites. ST8 was strongly correlated with site 192_F, 454_T. ST7 exhibited a strong correlation with site 51_A, 573_E, 648_S, and 664_A, and it was also associated with ST6 and site 544_N, 671_A, 738_B, 739_B, 740_B, and 774_Y. Additionally, a strong correlation between ST1 and site 142_S, 738_N, ST2 and site 2_K, 142_S, 738_N, as well as ST87 and site2_K, 738_N was demonstrated. Our findings contribute significantly to the understanding of the distribution, composition, and conservation of InlA in L. monocytogenes. These findings also suggest a potential role of InlA in supporting molecular epidemiological tracing efforts.

Background: Vaccinations are still the most effective means of preventing and controlling fish viral diseases, and cells are an important substrate for the production of a viral vaccine. Therefore, the rapid-stable growth and virus sensitivity of cells are urgently needed. Methods: Chinese perch brain 100th passage (CPB p100) were acclimated in a low serum with 5% FBS L-15 for 50 passages, then transferred to 8% FBS L-15 for 150 passages. Additionally, the morphology and cell type of CPB 300th passage (CPB p300) cells were identified. We analyzed the transfection efficiency and virus sensitivity of CPB p300 cells, and then optimized the conditions of ISKNV, SCRV, and LMBV multiplication in CPB cells. Results: CPB p300 cells were more homogeneous, and the spread diameter (20–30) µm in CPB p300 cells became the dominant population. The doubling time of CPB p300 was 1.5 times shorter than that of CPB p100.However, multiplication rate of CPB p300 was 1.37 times higher than CPB p100. CPB p300 cells were susceptible to ISKNV, SCRV, and LMBV, and the optimal conditions of ISKNV, SCRV, and LMBV multiplication were simultaneous incubation, 0.6 × 105 cells/cm2 and MOI = 0.1; infection at 48 h, 0.8 × 105 cells/cm2 and MOI = 0.01; simultaneous incubation, 0.7 × 105 cells/cm2 and MOI = 0.05, respectively. The time and economic costs of ISKNV, SCRV, and LMBV multiplication in CPB p300 cells were significantly reduced. Conclusions: The acquisition of CPB p300 cells laid a good material foundation for the production of ISKNV, SCRV, and LMBV vaccines.

Organoids are a class of multicellular structures with the capability of self-organizing and the characteristic of original tissues, they are generated from stem cells in 3D culture in vitro. Organoids can mimic the occurrence and progression of original tissues and widely used in disease models in recent years. The ability of tumor organoids to retain characteristic of original tumors make them unique for tumorigenesis and cancer therapy. However, the history of organoid development and the application of organoid technology in cancer therapy are not well understood. In this paper, we reviewed the history of organoids development, the culture methods of tumor organoids establishing and the applications of organoids in cancer research for better understanding the process of tumor development and providing better strategies for cancer therapy. The standardization of organoids cultivation facilitated the large-scale production of tumor organoids. Moreover, it was found that combination of tumor organoids and other cells such as immune cells, fibroblasts and nervous cells would better mimic the microenvironment of tumor progression. This might be important developing directions for tumor organoids in the future.

Abstract Prohibitins (PHBs) are a class of highly evolutionarily conserved proteins that widely distribute in prokaryotes and eukaryotes. PHBs function in cell growth and proliferation or differentiation, regulating metabolism and signaling pathways. PHBs have different subcellular localization in eukaryotes, but they are mainly located in mitochondria. In the mitochondria, PHBs stabilize the structure of the mitochondrial membrane and regulate mitochondrial autophagy, mitochondrial dynamics, mitochondrial biogenesis and quality control, and mitochondrial unfolded protein response. PHBs has shown to be associated with many diseases, such as mitochondria diseases, cancers, infectious diseases, and so on. Some molecule targets of PHBs can interfere with the occurrence and development of diseases. Therefore, this review clarifies the functions of PHBs in mitochondria, and provides a summary of the potential values in clinics.

Abstract Huntington’s disease (HD) is a neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein encoded from extra tracts of CAG repeats in exon 1 of the HTT gene. mHTT proteins are neurotoxic to render the death of neurons and a series of disease-associated phenotypes. The mHTT is degraded through autophagy pathway and ubiquitin–proteasome system (UPS). This study identified a small molecule, J3, as an autophagy inducer by high-content screening. The results revealed that J3 could inhibit mTOR, thus promoting autophagic flux and long-lived protein degradation. Further, J3 selectively lowered the soluble and insoluble mHTT but not wild type HTT levels in cell models. The HdhQ140 mice showed reduced HD-associated activity and loss of motor functions. However, administration of J3 showed increased activity and a slight improvement in the motor function in the open-field test, balance beam test, and rotarod tests. Furthermore, in vivo studies revealed that J3 decreased T-HTT and misfolded protein levels in the striatum and increased the levels of the medium spiny neuron marker DARPP-32. In addition, J3 showed good permeability across the brain-blood barrier efficiently, suggesting that J3 was a promising candidate for the treatment of HD.

Abstract To reveal the role of tephra in the deposition of black shale during periods of volcanic activity, we performed lithostratigraphic and geochemical analyses on 14 horizontally sliced samples drilled from a 2-cm-thick black shale interval in the lower Ch7 Member of the Upper Triassic Yanchang Formation, southern Ordos Basin. Results indicate that fewer plankton is preserved during tephra deposition than during periods of volcanic quiescence. With the decrease of volcanic activities and tephra deposition, the abundance of redox-sensitive trace elements (RSTEs) and biolimiting elements increases, while terrigenous elements gradually decrease, resulting in the improvement of organic matter (OM) preservation. Paleoenvironmental proxies suggest that the climate during the Late Triassic was generally warm and humid. However, subsequent intense volcanic eruptions may have caused climatic cooling that affected the water column, resulting in enhanced salinity, primary production, water stratification, and bottom water anoxia, leading to enhanced organic carbon production and preservation. Primary productivity and redox conditions controlled the accumulation of organic carbon. Although physical and chemical reactions relating to the deposition of tephra into water are short-lived, climate change induced by volcanic eruptions is the critical cause of black shale formation.

IntroductionTailings can cause extensive damage to soil structure and microbial community. Phytoremediation is an effective strategy for remedied tailings soil due to its environmentally friendly and low-cost advantage. Fungi play a crucial role in nutrient cycling, stress resistance, stabilizing soil structure, and promoting plant growth. However, the fungal community variation in phytoremediation remains largely unexplored.MethodsWe analyzed soil fungal community based on high-throughput sequencing during three plant species combined with urban sludge to remediate quartz tailings soil.ResultsThe results indicated that the fungal diversity was significantly increased with plant diversity, and the highest fungal diversity was in the three plant species combination treatments. Moreover, the fungal diversity was significantly decreased with the addition of urban sludge compared with plant treatments, while the abundance of potential beneficial fungi such as Cutaneotrichosporon, Apiotrichum, and Alternaria were increased. Notably, the fungal community composition in different plant species combination treatments were significant difference at the genus level. The addition of urban sludge increased pH, available phosphorus (AP), and available nitrogen (AN) content that were the main drivers for fungal community composition. Furthermore, the fungal networks of the plant treatments had more nodes and edges, higher connectedness, and lower modularity than plant combined with urban sludge treatments.ConclusionOur results showed that three plant species combined with urban sludge treatments improved fungal community and soil properties. Our results provide insights for quartz tailings soil remediation using plant-fungi- urban sludge.

Background and objective: In the process of tumor occurrence, evolution and development, immune, inflammation and nutrition are principal elements. The purpose of this study was to assess the prognostic value of systemic immune-inflammation index/albumin (SII/ALB) for patients with HBV-related hepatocellular carcinoma (HCC) who underwent transcatheter arterial chemoembolization (TACE). Methods: A total of 125 HBV-related HCC patients met inclusion criteria and were all enrolled in this research. The survminer R package. was used to calculate the best SII/ALB cutoff values. Chi-square test was used to analyze the relationship between SII/ALB and clinicopathological parameters. Kaplan-Meier curves and Cox proportional hazards models were used to investigate the effect of SII/ALB on overall survival (OS). Results: The cutoff value of SII/ALB was 2.992. In the derivation cohort, the patients were divided into SII/ALB-low (SII/ALB≤2.992) and SII/ALB-high (SII/ALB >2.992) groups. SII/ALB-high was found in patients with tumor size ≥3 (cm), white blood cell ≥3.5 (109/L), platelet ≥100 (109/L), neutrophils ≥1.8 (109/L), PT ≥ 14(s), SII ≥100, NLR ≥1.50 and PLR ≥60, (P

Viruses are non-living organisms that rely on host cellular metabolism to complete their life cycle. Siniperca chuatsi rhabdovirus (SCRV) has caused huge economic losses to the Chinese perch (Siniperca chuatsi) industry worldwide. SCRV replication is dependent on the cellular glutamine metabolism, while aspartate metabolism plays an important role in viral proliferation in glutamine deficiency. Herein, we investigated roles of asparagine metabolism in SCRV proliferation. Results showed that SCRV infection upregulated the expression of key enzymes in the aspartate metabolic pathway in CPB cells. And the key enzymes of malate-aspartic acid shuttle pathway upregulated during the virus invasion phase, and key enzymes of the asparagine biosynthesis pathway upregulated during the viral replication and release phase. When asparagine was added to the depleted medium, the SCRV copy number restored to 90% of those in replete medium, showing that asparagine and glutamine completely rescue the replication of SCRV. Moreover, inhibition of the aspartate- malate shuttle pathway and knockdown of the expression of key enzymes in the asparagine biosynthesis pathway significantly reduced SCRV production, indicating that the aspartic acid metabolic pathway was required to the replication and proliferation of SCRV. Above results provided references for elucidating pathogenic mechanism of SCRV by regulation of aspartate metabolism.

Semi-solid powder rolling (SSPR) is widely used to produce alloy strips with fine grains and excellent performances in the automotive, aerospace and shipbuilding industries. During SSPR, powder temperature, as a very important parameter, greatly affects strips’ microstructures and mechanical properties, which have been investigated by many researchers, but its effect on the forming process and mechanism has rarely been studied. Therefore, based on online experimental detection and transient simulation, the microstructures, strip temperatures, relative densities and rolling forces at different conditions were, respectively, measured, calculated, compared and analyzed in order to study the deformation process and mechanism during SSPR. The result shows that with the increase in powder temperature, the strip temperature and relative density increase, while the rolling force decreases. The grains of the strips are refined after SSPR, and fine and dense microstructures are obtained at 600 °C, which is the optimum powder temperature. In the main deformation sections (II and III), when the contact normal force exists and reaches a maximum, the relative density and rolling force increase rapidly. At these sections, the strips rolled at 600 °C are mainly in a porous solid state, and powder crushing dominates the strip deformation. Therefore, SSPR at 600 °C and below can be considered porous or powder hot rolling, integrating powder crushing, solidification, deformation, densification and grain coarsening. Moreover, as the simulated values are basically consistent with experimental values, the thermomechanical coupling model based on the Fourier equation and its parameters are confirmed to be reasonable.

Background: Largemouth bass birnavirus (LBBV) disease outbreaks in largemouth bass fingerlings lead to high mortality in China. Therefore, the development of immersion immunization strategies is paramount. Methods: An avirulent LBBV strain was screened using a fish challenge assay. The proliferation dynamics of the avirulent strain were determined in vitro and in vivo. The efficacy of the avirulent vaccine was evaluated using immune gene expression, viral load, and a virus challenge, and the safety was also assessed using a reversion to virulence test. Results: An avirulent virus strain, designated as largemouth bass birnavirus Guangdong Sanshui (LBBV-GDSS-20180701), was selected from five fish birnavirus isolates. The proliferation peak titer was 109.01 TCID50/mL at 24 hpi in CPB cells and the peak viral load was 2.5 × 104 copies/mg at 4 dpi in the head kidneys and spleens of largemouth bass. The largemouth bass that were immersed within an avirulent vaccine or injected with an inactivated vaccine were protected from the virulent LBBV challenge with a relative percent survival (RPS) of 75% or 42.9%, respectively. The expression levels of IL-12, MHCI, MHCII, CD8, CD4, and IgM in the avirulent group were significantly upregulated at a partial time point compared to the inactivated vaccine group. Moreover, the viral load in the avirulent vaccine group was significantly lower than those in the inactivated vaccine group and control group using real-time PCR. Conclusions: LBBV-GDSS-20180701 is a potential live vaccine candidate against LBBV disease.

Red sea bream (Pagrosomus major) is one of the most popular farmed marine teleost fish species. Fish cell lines are becoming important research tool in the aquaculture field, and they are suitable models to study fish virology, immunology and toxicology. To obtain a Pagrosomus major cell line for biological studies, a continuous cell line from brain of red sea bream (designated as RSBB cell line) was established and has been successfully subcultured over 100 passages. The RSBB cell line predominantly consisted of fibroblast-like cells and multiplied well in M199 medium supplemented with 10% fetal bovine serum at 28 °C. Karyotyping analysis indicated that the modal chromosome numbers of RSBB cells was 48. After transfection with pEGFP-N1, RSBB cells showed bright green fluorescence with a transfection efficiency approaching 8%. For toxicology study, it was demonstrated that metal Cd could induce cytotoxic effects of RSBB cells, accompanied with a dose-dependent MTT conversion capacity. Morphologically, cells treated with metal Cd produced rounding, shrinking and detaching and induced both cell apoptosis and necrosis. For virology study, the RSBB cells were highly susceptible to Nervous necrosis virus (NNV) and Singapore grouper iridovirus (SGIV) with steady titers (i.e., 108.0~8.3 TCID50 mL−1 and 107.0~7.2 TCID50 mL−1 respectively). Furthermore, an obvious cytopathic effect (CPE) could be observed in RSBB cells infected with Infectious spleen and kidney necrosis virus (ISKNV) and Siniperca chuatsi rhabdoviruses (SCRV). Meanwhile, all the infections were confirmed by polymerase chain reaction. The new brain cell line developed and characterized from red sea bream in this study could be used as an in vitro model for fish studies in the fields of toxicology and virology.

In-situ conversion technology has been more popular lately as an effective way to realize the industrial development of extensive medium- and low-mature shale oil/oil shale resources in China. The Ordos Basin has been recognized as the main basin containing the largest in-situ conversion recoverable resources of China. Researchers have revealed the hydrocarbon generation kinetics of low mature oil shales in the 7th Member of the Yanchang Formation (Chang 7 Member). However, the kinetics of medium mature shales may be different from those of low mature shales, and they can also be used as potential targets for in-situ conversion. At present, there is a lack of research on the in-situ hydrocarbon generation kinetics of medium- and low-mature shale oil/oil shale. In this paper, open system pyrolysis experiments were carried out on natural shales and shale samples derived from semi-open system pyrolysis with different maturities in the Chang 7 Member of the Ordos Basin respectively. Using the parallel first-order reaction theory, the frequency factor of low-mature shale was calculated to be 5.47 × 1010 s−1, and the distribution of activation energy ranged from 38 kcal/mol to 61 kcal/mol. The main peak of activation energy was 49 kcal/mol, and accounted for 66.91% of all shales. With the increase in maturity, the average activation energy becomes higher, and therefore more in-situ conversion energy is needed. At the same time, the hydrocarbon generation potential characterized by S2 peak of pyrolysis decreases during the maturation process. The activation energy is divided into three groups according to its distribution characteristics: low, main peak and high activation energy groups, representing 52 kcal/mol respectively. The proportion of low and high activation energy groups increased with the increase in maturity, while the proportion of main peak activation energy groups decreased. When the kinetic parameters are extrapolated to the condition of in-situ conversion, it is better to choose shales with low maturity (RO

The aim of this study was to investigate whether and how exosomal miR-205-5p regulated angiogenesis and nasopharyngeal carcinoma (NPC) metastasis. We found that up-regulated serum exosomal miR-205-5p levels were associated with NPC progression and worse overall survival of NPC patients. miR-205-5p over-expression significantly increased tube formation, wound healing, migration and invasion of NPC cells, and lung metastasis of NPC tumors, whereas miR-205-5p inhibition had opposite effects. Exosomal miR-205-5p from NPC cells promoted the migration, tube formation, and microvessel density (MVD) of HUVECs in vitro and in vivo. Furthermore, bioinformatics-, luciferase reporter-, and biotinylated miR-205-5p-based pull-down assays indicated that miR-205-5p directly bound to the 3′ UTR of desmocollin-2 (DSC2). Exosomal miR-205-5p targeted DSC2 to enhance the EGFR/ERK signaling and MMP2/MMP9 expression, promoting angiogenesis and NPC metastasis, which was abrogated by DSC2 over-expression. Finally, the levels of miR-205-5p transcripts were positively correlated with MVD but negatively with DSC2 expression in NPC tissues, and patients with miR-205high/DSC2low NPC had worse overall survival. In conclusion, exosomal miR-205-5p promotes angiogenesis and NPC metastasis by targeting DSC2 to enhance EGFR/ERK signaling and MMP expression. This exosomal/miR-205-5p/EGFR/ERK axis may be a new therapeutic target for intervention of NPC metastasis.

Listeria monocytogenes is an important pathogen that can cause listeriosis. Despite the growing recognition of Listeria spp. as a foodborne and environmental pathogen, the understanding of its prevalence and characteristics of Listeria spp. in the marine environment remains unknown. In this study, we first investigated the genetic and phenotypic characteristics of Listeria species isolated in a coastal city in China. The findings revealed that the sequence type 87 (ST87) L. monocytogenes, a prevalent clinical and seafood strain in China, dominates in recreational beach sands and possesses a notable biofilm-forming capacity in seawater. The presence of ST87 L. monocytogenes in coastal environments indicates the potential health risks for both recreational activities and seafood consumption. Moreover, the ST121 isolates from sand had a versatile plasmid encoding multifunctional genes, including uvrX for UV resistance, gbuC for salt resistance, and npx for oxidative resistance and multiple transposases, which potentially aid in survival under natural environments. Black-headed gulls potentially facilitate the spread of L. monocytogenes, with similar ST35 strains found in gulls and beach sand. As a reservoir of microbes from marine environments and human/animal excrement, coastal sand would play an important role in the spread of L. monocytogenes and is an environmental risk for human listeriosis.

The reservoir properties of low–medium-maturity shale undergo complex changes during the in situ conversion process (ICP). The experiments were performed at high temperature (up to 450 °C), high pressure (30 MPa), and a low heating rate (0.4 °C/h) on low–medium-maturity shale samples of the Chang 7 Member shale in the southern Ordos Basin. The changes in the shale composition, pore structure, and reservoir properties during the ICP were quantitatively characterized by X-ray diffraction (XRD), microscopic observation, vitrinite reflectance (Ro), scanning electron microscopy (SEM), and reservoir physical property measurements. The results showed that a sharp change occurred in mineral and maceral composition, pore structure, porosity, and permeability at a temperature threshold of 350 °C. In the case of a temperature > 350 °C, pyrite, K-feldspar, ankerite, and siderite were almost completely decomposed, and organic matter (OM) was cracked into large quantities of oil and gas. Furthermore, a three-scale millimeter–micrometer–nanometer pore–fracture network was formed along the shale bedding, between OM and mineral particles and within OM, respectively. During the ICP, porosity and permeability showed a substantial improvement, with porosity increasing by approximately 10-times and permeability by 2- to 4-orders of magnitude. Kerogen pyrolysis, clay–mineral transformation, unstable mineral dissolution, and thermal stress were the main mechanisms for the substantial improvement in the reservoir’s physical properties. This study is expected to provide a basis for formulating a heating procedure and constructing a numerical model of reservoir properties for the ICP field pilot in the Chang 7 shale of the Ordos Basin.

ObjectiveSix anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), including one domestic (ensartinib) and five imported ALK-TKIs (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib), have been recommended as first-line treatments for advanced ALK-positive NSCLC in China. This study sought to examine the cost-effectiveness of these six novel therapies in Chinese patients.Material and methodsWe constructed a Markov model to compare the cost-effectiveness of the six ALK-TKIs as a first-line treatment for patients with advanced ALK-positive NSCLC from the perspective of the Chinese healthcare system. Transition probabilities were estimated by synthesizing data from the PROFILE 1,029 trial and a network meta-analysis. Health state utilities and costs were sourced from published literature, publicly available national databases, and local general hospitals. The robustness of model was assessed via deterministic sensitivity analyses and probabilistic sensitivity analyses.ResultsCompared with crizotinib, ensartinib achieved additional 0.12 quality-adjusted life-year (QALY) with marginal costs of $3,249, resulting in an incremental cost-effectiveness ratio (ICER) of $27,553/ QALY. When compared with ceritinib and brigatinib, ensartinib achieved additional 0.06 and 0.03 QALYs with substantially reduced costs. When compared with lorlatinib and alectinib, ensartinib was associated with a lower QALY and decreased total costs; the ICERs for lorlatinib and alectinib were $934,101/ QALY and $164,888/ QALY, respectively.ConclusionFor Chinese patients with advanced ALK-positive NSCLC, ensartinib was a cost-effective option compared with crizotinib, and was a dominant alternative to ceritinib and brigatinib. Although lorlatinib and alectinib were associated with prolonged survival compared with ensartinib, they were less cost-effective than ensartinib due to the overwhelming total costs.

ObjectiveTo compare the cost-effectiveness of undertaking low-dose computed tomography (LDCT) screening for early detection of lung cancer (LC) with different frequencies within the healthcare system of China, and estimate the additional national healthcare expenditure and five-year LC mortality associated with different screening frequencies.Material and methodsA Markov model was established using national LC epidemiological data from the Chinese Center for Disease Control and Prevention, demographic data from the Chinese Statistical Yearbook, and cost and effectiveness data mainly from the Cancer Screening Program in China. The model included thirty sex-specific screening strategies, which were classified by initial screening age (30, 35, 40, 45, and 50), and screening intervals (intervals at single time point, 1, 2, 5, 10, and 20 years). The main model outputs were incremental cost-effectiveness ratios (ICERs), additional national healthcare expenditure and five-year LC mortality.ResultsThe ICERs for LDCT screening strategies vs. non-screening strategy ranged from $16,086 per quality-adjusted life-year (QALY) to $3,675,491 per QALY in the male cohort, and from $36,624 per QALY to $5,943,556 per QALY in the female cohort. The annual increment national healthcare expenditures related to LDCT screening were varied from $0.25 to $13.39 billion, with the lower cost in the cohort with older screening ages and lower screening frequencies. More frequent screening with LDCT was associated with a greater reduction in LC death: an annual LDCT screening was linked to an estimated reduction in five-year LC death by 27.27–29.07%, while a one-off screening was linked to a reduction by 5.56–5.83%.ConclusionUnder a willingness-to-pay (WTP) threshold of three times the Chinese gross domestic product (GDP) per capita (US $37,654), annual screening with an initiating age at 50 was most cost-effective in both male and female cohorts. By taking into account both the national healthcare expenditures and the effect of LDCT screening, our study results support undertaking LDCT screening annually from 50 years old in general populations.

The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the associations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization. The seropositive rates of IgG and IgM were 29.6% and 48.1%, respectively, in the first week, and plateaued within five weeks. For the patients discharged from the hospital, the IgM decreased slowly, while high levels of IgG were maintained at around 188 AU·mL−1 for the 12 weeks since illness onset. In contrast, in the patients who subsequently died, IgM declined rapidly and IgG dropped to 87 AU·mL−1 at the twelfth week. Elevated interleukin-6, interleukin-8, interleukin-10, interleukin-1β, interleukin-2R, and tumor necrosis factor-α levels were observed in the deceased patients in comparison with the discharged patients, and 12.5% of the association between IgG level and mortality risk was mediated by these cytokines. Our study deciphers the temporal profiles of SARS-CoV-2-specific antibodies within the 12 weeks since illness onset and indicates the protective effect of antibody response on survival, which may help to guide prognosis estimation.

Based on 991 groups of analysis data of shale samples from the Lower Member of the Cretaceous Eagle Ford Formation of 1317 production wells and 72 systematic coring wells in the U.S. Gulf Basin, the estimated ultimate recovery (EUR) of shale oil and gas of the wells are predicted by using two classical EUR estimation models, and the average values predicted excluding the effect of engineering factors are taken as the final EUR. Key geological factors controlling EUR of shale oil and gas are fully investigated. The reservoir capacity, resources, flow capacity and fracability are the four key geological parameters controlling EUR. The storage capacity of shale oil and gas is directly controlled by total porosity and hydrocarbon-bearing porosity, and indirectly controlled by total organic carbon (TOC) and vitrinite reflectance (Ro). The resources of shale oil and gas are controlled by hydrocarbon-bearing porosity and effective shale thickness etc. The flow capacity of shale oil and gas is controlled by effective permeability, crude oil density, gas-oil ratio, condensate oil-gas ratio, formation pressure gradient, and Ro. The fracability of shale is directly controlled by brittleness index, and indirectly controlled by clay content in volume. EUR of shale oil and gas is controlled by six geological parameters: it is positively correlated with effective shale thickness, TOC and fracture porosity, negatively correlated with clay content in volume, and increases firstly and then decreases with the rise of Ro and formation pressure gradient. Under the present upper limit of horizontal well fracturing effective thickness of 65 m and the lower limit of EUR of 3×104 m3, when TOC

Objective: Domestic PD-1inhibitor tislelizumab has emerged as a promising treatment for Chinese patients with driver-negative advanced or metastatic non-small cell lung cancer (NSCLC). The purpose of our study to evaluate whether tislelizumab is cost-effective as a second- or third-line treatment for this population compared with docetaxel (conventional chemotherapy) and nivolumab (imported PD-1inhibitor), from the perspective of the Chinese healthcare system.Material and Methods: A Markov model with a 3-week Markov cycle and a 30-year time horizon was built to compare the cost-effectiveness of second- or third-line tislelizumab versus docetaxel and nivolumab. Transition probabilities, including disease progression, survival, and adverse events (AEs)-related treatment discontinuation event, were estimated from the clinical trials. Costs and health utilities were collected from local hospitals, public database and published literature.Results: Compared with docetaxel, tislelizumab provided an additional 0.33 quality-adjusted life-years (QALYs) (1.37 vs. 1.04 QALYs) at an incremental cost of $9,286 ($23,646 vs. $14,360) for Chinese patients with driver-negative advanced or metastatic NSCLC, resulting in an incremental cost-effectiveness ratio (ICER) of $27,959/QALY under the WTP threshold of $35,663/QALY used in the model. Compared with nivolumab, tislelizumab was associated with a lower cost ($23,646 vs. $59,447) and higher QALYs (1.37 vs. 1.20 QALYs), resulting in its dominance of nivolumab.Conclusion: From the perspective of the Chinese healthcare system, domestic PD-1inhibitor tislelizumab immunotherapy represents a cost-effective treatment strategy compared with conventional docetaxel chemotherapy and imported PD-1inhibitor nivolumab immunotherapy in the treatment of driver-negative advanced or metastatic NSCLC beyond the first-line setting. In the era of “Universal Medical Insurance System”, the rational use of domestic anticancer drugs guided by cost-benefit evidence would be an effective means to balance the limited expenditure of medical insurance fund and the growing demand for cancer treatments.

Objective: To investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody tislelizumab to first-line pemetrexed-platinum chemotherapy in (1) a study population of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (nsqNSCLC) and without known sensitizing EGFR mutations or ALK rearrangements and (2) its subgroups from the perspective of Chinese healthcare system.Material and Methods: Separate Markov models were constructed for the entire study population and its subgroups; 10,000 patients with locally advanced or metastatic nsqNSCLC and without driver gene mutations were simulated in the first-line tislelizumab plus pemetrexed-platinum (TPP) arm and first-line pemetrexed-platinum (PP) arm, respectively. Transition probabilities were extracted from the RATIONALE 304 trial. Public health state utilities and costs were obtained from published literature, public national databases, and local general hospitals. The main outputs were incremental cost-effectiveness ratios (ICERs). The ICERs were compared to a willingness-to-pay threshold of $35,663 per quality-adjusted life-years (QALYs) to determine the cost-effective treatment. Sensitivity analyses were employed to assess the uncertainty in the model.Results: For the entire patient population, first-line TPP versus PP use increased the effectiveness by 0.99 QALYs and healthcare costs by $28,749, resulting in an ICER of $28,749/QALY that was lower than the prespecified WTP threshold. For patient subgroups, first-line TPP conferred the greatest survival benefit in patients with PD-L1 expression ≥50%, followed by patients with liver metastasis and those who are current or former smokers. Overall, the ICERs for the first-line TPP versus PP ranged from $27,018/QALYs to $33,074/QALYs, which were consistently below the WTP threshold.Conclusion: For Chinese patients with locally advanced or metastatic nsqNSCLC who had no known sensitizing EGFR mutations or ALK rearrangements, adding the Chinese-developed anti-PD-1 antibody tislelizumab to the first-line pemetrexed-platinum chemotherapy was cost-effective regardless of their baseline characteristics.

An experimental and analytical investigation of ultrahigh-performance concrete (UHPC) plate-concrete-filled steel tubular (CFST) laced composite columns are presented in this study. A total of 11 stub specimens under axial compression are conducted to quantify the column failure mechanism. Experimental results indicate that the compressive behavior in the UHPC plate dominated the failure mechanism of the UHPC composite columns, and the failure mode is dependent on the peak strain of the UHPC plate and CFST limb. The two main parameters in the tests are the thickness of the steel tube (t) and UHPC plates (tp), which significantly enhance the bearing capacity of UHPC composite columns. Herein, the finite element standard model is established to investigate the influence of various parameters on the compressive behavior of UHPC composite columns. The diameter of the steel tube D is the most sensitive parameter affecting the structural compressive performance, while the ratio of steel reinforcing bars has an ignorable influence on the compressive strength. Based on the ultimate limit states and parametric analysis, a unified formula for predicting the strength of UHPC composite columns is proposed, which is generally in good agreement with the experimental results.

Objective: Pembrolizumab plus chemotherapy is recommended as the first-line treatment for advanced oesophageal cancer. The objective of this study is to evaluate the cost-effectiveness of pembrolizumab plus chemotherapy as first-line therapy for advanced oesophageal cancer from the healthcare system perspective in China.Methods: Based on the KEYNOTE-590 trial, a Markov model was constructed to estimate the cost and effectiveness of pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. One-way, probabilistic sensitivity analyses (PSA), and subgroup analyses were adapted to test the model robustness.Result: Compared with the placebo group, pembrolizumab group obtained an additional 1.05 QALY, but the cost was also increased by $121,478.76. The ICER was $115,391.84 per QALY gained, which was higher than the willingness-to-pay (WTP) of $31,304.31. The results of One-way sensitivity analyses showed that the ICER was sensitive to the hazard ratio of PFS and per cycle cost of pembrolizumab. At a WTP threshold of $31,304.31, the probability of pembrolizumab plus chemotherapy being cost-effective was 0%.Conclusion: From the perspective of China healthcare system, pembrolizumab plus chemotherapy as first-line treatment is not cost-effective for patients with advanced oesophageal cancer compared with placebo plus chemotherapy.

Objective: The objective of this study is to systematically review the economic evaluations of dapagliflozin in the treatment of patients with heart failure (HF) and describe their general and methodological features.Methods: This systematic review followed the PRISMA guidelines. MEDLINE/PubMed, Website Of Science, Embase, The Cochrane Library, ScienceDirect, CNKI, and Wanfang databases were searched to collect relevant studies, and the retrieval time ended on 31 October 2021. Articles on the economic evaluation of dapagliflozin in the treatment of heart failure were included. Secondary studies, incomplete economic indicators, and non-English-language and non-Chinese-language studies were excluded. Standard drug treatment was selected as the comparison. Basic characteristics, methods, and main results were extracted and analyzed systematically.Result: A total of eight studies were identified, and the overall quality was accepted, which were performed in nine developed countries (Austria, United States, Korea, Japan, Singapore, Spanish, Germany, and United Kingdom) and three developing countries (the Philippines, Thailand, and China). With the exception of the Philippines, the remaining countries considered that dapagliflozin was cost effective. In the analyses of all included studies, the incremental cost-effectiveness ratios were most sensitive to the cost of dapagliflozin, cardiovascular mortality, the duration of dapagliflozin effectiveness, and the probability of HF hospitalization.Conclusion: Dapagliflozin in the treatment of patients with heart failure with reduced ejection fraction was considered cost effective. Further studies are needed to evaluate the comprehensive value of dapagliflozin on HF.