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Abstract Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism. RIMKLA expression was reduced in livers of human and mouse with NAFLD. Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice. Hepatocyte-specific RIMKLA knockout aggravated high-fat diet (HFD)-induced dysregulated glucose/lipid metabolism in mice. Mechanistically, RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1 (BHMT1) at threonine 45 (Thr45) site. Upon phosphorylation at Thr45 and activation, BHMT1 eliminated homocysteine (Hcy) to inhibit the activity of transcription factor activator protein 1 (AP1) and its induction on fatty acid synthase (FASn) and cluster of differentiation 36 (CD36) gene transcriptions, concurrently repressing lipid synthesis and uptake in hepatocytes. Thr45 to alanine (T45A) mutation inactivated BHMT1 to abolish RIMKLA’s repression on Hcy level, AP1 activity, FASn/CD36 expressions, and lipid deposition. BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes. In summary, RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake. Under obese condition, inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.

Abstract Background Extracellular adenosine triphosphate (ATP) is an important signal molecule. In previous studies, intensive research had revealed the crucial roles of family with sequence similarity 3 member A (FAM3A) in controlling hepatic glucolipid metabolism, islet β cell function, adipocyte differentiation, blood pressure, and other biological and pathophysiological processes. Although mitochondrial protein FAM3A plays crucial roles in the regulation of glucolipid metabolism via stimulating ATP release to activate P2 receptor pathways, its mechanism in promoting ATP release in hepatocytes remains unrevealed. Methods db/db, high-fat diet (HFD)-fed, and global pannexin 1 (PANX1) knockout mice, as well as liver sections of individuals, were used in this study. Adenoviruses and adeno-associated viruses were utilized for in vivo gene overexpression or inhibition. To evaluate the metabolic status in mice, oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT), insulin tolerance test (ITT), and magnetic resonance imaging (MRI) were conducted. Protein–protein interactions were determined by coimmunoprecipitation with mass spectrometry (MS) assays. Results In livers of individuals and mice with steatosis, the expression of ATP-permeable channel PANX1 was increased (P

API standard threads are the most commonly used thread configurations for drill pipe joints in the petroleum industry. Recently with the increasing application of horizontal wells and extended-reach wells in drilling engineering, drill pipe joint threads are subjected to complex loads, and drill pipe joint thread breakage accidents occur frequently. The API NC38 threaded pair used in the SU36-8-4H2 well suffered a fracture accident. Macroscopic analysis found that the fracture sites were located near the root of the first engagement pin-thread where the stress was greatest. Therefore, it is necessary to find an alternative method to reduce the largest stress of NC38 threads. Then, a new design method of unequal taper thread (UTT) pairs is proposed that the taper of pin thread, slightly smaller than the taper of matched-box thread, is not equal to one of box-thread. In the UTT pairs of API NC38 thread, the taper of box thread is kept as the standard taper of 1:6, but the taper of pin thread is, respectively, 1:6.1 (UTT-I), 1:6.2 (UTT-II), 1:6.3 (UTT-III) and 1:6.4 (UTT- IV). The 3D finite element models of four UTT pairs and one standard pair based on NC38 thread were developed, and the mechanical properties of five thread pairs bearing such typical working loads as torque, axial compression, axial tension, bending moment, internal and external pressure, were analyzed. The results show that four UTT pairs are superior to the standard pair of API NC38, and UTT-III has the most performance in all of four UTT pairs. Compared with the standard pair of API NC38, UTT-III pair can improve the bearing capacity such as torsion strength, compression strength, tensile strength, bending strength, strength against internal and external pressure, by 24.8%, 13.2%, 22%, 9.99% and 14.2%, respectively. The new design method of UTT pair enhances the bearing capacity of API NC38 thread, and has been applied in Changqing Drilling Company of CNPC Chuanqing Drilling Engineering Company Limited. The UTT-thread pair method is not only applicable for API series threads to improve the connection performance, but also suitable for various non-API taper connection threads to promote existing working ability such as air tightness, stress corrosion resistance, fatigue resistance et al.

Background: In coping with the coronavirus disease 2019 (COVID-19) epidemic, cities adopted social isolation and lockdown measures; however, little is known about the impacts of these restrictions on household food security. Objective: This study provides a timely assessment of household food insecurity (HFI) in the Chinese city of Wuhan during the COVID-19 epidemic period and also investigates its determinant factors. Design: We collected valid data on food insecurity from 653 households in Wuhan via an online questionnaire in March 2020. The Household Food Insecurity Access Scale Score (HFIASS) was used to measure HFI, and a multiple linear regression model was used to determine the HFIASS. Results: The mean HFIASS in Wuhan was 9.42 (standard deviation: 5.82), with more than 50% of the households had an HFIASS < 9. Compared with normal conditions, lockdown measures had a huge negative impact on household food security. The results revealed that socio-demographic characteristics remained the underlying determinants of HFIASS during the epidemic. Households in Wuhan with local Hukou (city household registration) and self-owned property had a lower risk of food insecurity. Discussion and conclusion: After the restriction of conventional food access channels, intermediary food purchase methods such as group purchasing, shopping with the help of neighborhood committees, property management agents, and volunteers became the most important or the only channel for residents to access food. There were similarities in the use of these intermediary channels. Based on the probability that the epidemic will continue and the probability of similar public health-related outbreaks in the future, the study calls for a more resilient and responsive sustainable food supply system by harnessing the capacity of communities, e-commerce and rapid logistics.

Objective: To explore the molecular targets and associated potential pathways of Lycii Fructus (LF, Gou Qi Zi, 枸杞子) in the treatment of retinitis pigmentosa (RP) by the approaches of network pharmacology and bioinformatics. Methods: The potential blood-entry active ingredients and targets of LF were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). RP-related gene targets were retrieved through disease comprehensive databases. Protein-protein interaction (PPI) network of LF component-targets and RP disease-targets was constructed by STRING, and the intersection of the 2 networks was extracted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of theintersection network were conducted by Database for Annotation, Visualization and Integrated Discovery (DAVID). CytoHubba was used to screen the key targets. Results: A total of 188 chemical constituents related to LF was retrieved from TCMSP database. 45 active ingredients were screened according to pharmacokinetic parameters oral bioavailability (OB) and drug similarity (DL). 36 active ingredients were further screened and 201 targets related to these constituents were obtained. 206 target genes directly related to RP were obtained from the disease comprehensive databases, and 89 genes were obtained from the intersection of component-target and disease-target PPI network. These genes were mainly involved in intracellular signal transduction, GTPase activity regulation, cell morphology regulation, and other biological processes. Molecular functions were mainly related to Rho guanine nucleotide exchange factor activity, GTPase activator activity, receptor signal protein serine/threonine kinase activity and so on. They were enriched in the cytoplasm, cell membrane, Golgi apparatus, and other regions. The mechanism was related to cell cycle pathways, neurotrophin signaling pathways, Ras signaling pathways, and so on. 10 key gene targets of LF in the treatment of RP were screened. Conclusions: The material basis for LF to exert its pharmacodynamic effect is 36 active ingredients such as cycloartenol, mandenol, and so on. The key targets of LF in the treatment of RP include 10 genes, such as Rho, PAK, and so on. The main mechanism is related to the regulation of the Ras signaling pathway, neurotrophin signaling pathway, cell cycle related pathway, and other signaling networks. Keywords: Network pharmacology, Retinitis pigmentosa, Lycii Fructus (Gou Qi Zi, 枸;杞;子;), Molecular mechanism, Target, Signaling pathway

As a former treaty port and a current Special Economic Zone (SEZ) in China, Shantou occupies unique position in China's interaction with colonialism and globalisation. Through an analysis of English translations in the linguistic landscape (LL) in Shantou, it was found that international, local and regional factors work together to shape the city's LL. Shantou's resistance to the hegemony of English is encoded in the creative strategies that are adopted in translation, which include transliteration punning, cultural manipulation and hybrid translation. Drawing on the model of English as a lingua franca (ELF), this paper analyses how these strategies reflect the creative, flexible potential of English. These creative strategies can be interpreted as an expression of foreignisation, through which the sign writer consciously deviates from established norms in English to preserve local cultural traits and articulate local identity. Since LL reflects how meaning is negotiated in authentic social settings, incorporating LL projects in the classroom allows language learners and translator trainees to assume an active role in meaning negotiation in their sociolinguistic context. Ultimately, LL projects can empower students to exercise agency in articulating their own culture and constructing their social identity.

An analysis was carried out in this paper on the bearing capacity of pier pile and seismic performance rule when the low-pile cap is increased by 1 meter, 2 meters, and 3 meters. The bottom of the pile cap of pier no. 11 of Minjiang River bridge faces three “lows”: 7.6 meters lower than island, 4.6 meters lower than natural river bed, and 6.5 meters lower than low water level. The numerical simulation method is adopted to input three seismic waves of Wolong, Bajiao, and EL to evaluate the bearing capacity of pier and pile under strong earthquakes. Using the standard formula and numerical simulation method, it is observed that the bending moment and axial force of bridge pier show an insignificant change under different seismic waves when the pile cap is increased by 0–3 meters. With peak ground acceleration increased to 0.35 g, the vertical bearing capacity and flexural capacity of pier and pile gratify the requirements; however, the pile foundation will be subject to compression and bending damage.

A/J mice were found to have amino acid differences in Naip5, one of the NOD-like receptors (NLRs) involved in the cytosolic recognition of pathogen-associated molecular patterns and one of the adaptor proteins for caspase-1 activation. This defect was associated with a susceptibility to Legionella infection, suggesting an important role for Naip5 in the immune response also to other intracellular pathogens, such as Mycobacterium leprae. In this study, the immune responses of macrophages from A/J mice against M. leprae were compared to those of macrophages from C57BL/6 mice. Infection with M. leprae induced high levels of TNF-α production and NF-κB activation in A/J and C57BL/6 macrophages. Caspase-1 activation and IL-1β secretion were also induced in both macrophages. However, macrophages from A/J mice exhibited reduced caspase-1 activation and IL-1β secretion compared to C57BL/6 macrophages. These results suggest that NLR family proteins may have a role in the innate immune response to M. leprae.

RIPK 2 is adapter molecule in the signal pathway involved in Toll-like receptors. However, there has been no reported association between receptor-interacting serine/threonine kinase 2 (RIPK 2) expression and the infectious diseases involving mycobacterial infection. This study found that its expression was down-regulated in the footpads and skin but was up-regulated in the liver of Mycobacterium leprae-infected nu/nu mice compared with those of the M. leprae non-infected nu/nu mice. It was observed that the interlukin-12p40 and interferon-γ genes involved in the susceptibility of M. leprae were down-regulated in the skin but were up-regulated in the liver. Overall, this suggests that regulation of RIPK 2 expression is tissue-specifically associated with M. leprae infection.

AIM: To understand the publication status, research trends, and cutting-edge and hot topics in this field by conducting a bibliometrics analysis of relevant literatures on the pathogenesis of primary open angle glaucoma(POAG)in the past 30 a.METHODS:A total of 986 relevant literatures on the pathogenesis of POAG published on the core databases of China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)from 1 September 1993 to 1 September 2023 were retrieved. CiteSpace(6.2.R.4)and VOSviewer(1.6.18)software were used to conduct knowledge graph analysis on the retrieved literature, including publication volume, author, research institution, country/region, and keywords.RESULTS:The United States(243 articles)has the highest number of publications, followed by China(121 articles). The foreign institution with the highest number of publications is Harvard University(37 articles), while domestic institutions such as Zhongshan Ophthalmic Center, Sun Yat-sen University, ophthalmology department of Xuanwu Hospital of Capital Medical University, and Peking University First Hospital tied for the highest number of publications. Louis R. Pasquale(21 articles)is the most prolific English author. Wang Ningli is the most active Chinese researcher in this field. Keywords include trabecular meshwork, intraocular pressure, aqueous humor, glucocorticoid, hemorheology, etc.CONCLUSION: The research on the pathogenesis of POAG is in a period of vigorous development. The United States has the largest number of publications in this field, and Harvard University is a leading institution in this field. The research focus in the field of POAG has shifted from the structural aspect to the genetic level, and gene research and traditional Chinese medicine treatment have broad application prospects in this field.

Lycium barbarum L. and Salvia miltiorrhiza Bunge (Gouqi and Danshen, LS) have led to their inclusion in the pharmacopoeia and healthcare systems of numerous countries globally. Traditional herbs known as LS are used in China to treat retinitis pigmentosa (RP). However, the mechanism is not clear. This study is to investigate the mechanism by which LS improves RP using rd10 mice as a model. LS extract was used to treat the rd10 mice for four weeks. Fundus photographs, optical coherence tomography, electroretinography, histopathological examination, TUNEL apoptosis assay, digital PCR analysis, western blotting, and immunofluorescence double staining were performed. The outer nuclear layer (ONL) thickness of the retina was significantly increased by the LS extract, improving atrophy, and both the ONL and the retinal pigment epithelium (RPE) layer were visible. Following treatment with LS extract, there was a notable increase in the magnitudes of ERG a- and b-waves in the retina, along with a significant reduction in the quantity of TUNEL-positive cells. Additionally, LS extract significantly reduced the levels of ER stress-related factors in rd10 mice. The results of immunofluorescence double staining further confirm that LS extract inhibits the GRP78/PERK/ATF4/CHOP pathway. In this study, the protective effects of LS extract on the retina were uncovered, suggesting that its mechanism could involve decreasing retinal cell apoptosis through the inhibition of the ER stress pathway. [Display omitted] • Lycium barbarum L. and Salvia miltiorrhiza Bunge extract improve retinal morphology and function. • Regulation of the endoplasmic reticulum stress inhibit the cell apoptosis in the retina. • Lycium barbarum L. and Salvia miltiorrhiza Bunge extract against endoplasmic reticulum stress in rd10 mice was first explored. [ABSTRACT FROM AUTHOR]

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A one-step dual flow immunochromatographic assay (DICGA), based on a competitive format, was developed for simultaneous quantification of ochratoxin A (OTA) and zearalenone (ZEN) in corn, wheat, and feed samples. The limit of detection for OTA was 0.32 ng/ml with a detection range of 0.53‒12.16 ng/ml, while for ZEN it was 0.58 ng/ml with a detection range of 1.06‒39.72 ng/ml. The recovery rates in corn, wheat, and feed samples ranged from 77.3% to 106.3% with the coefficient of variation lower than 15%. Naturally contaminated corn, wheat, and feed samples were analyzed using both DICGA and liquid chromatography-tandem mass spectrometry (LC-MS/MS) and the correlation between the two methods was evaluated using a regression analysis. The DICGA method shows great potential for simple, rapid, sensitive, and cost-effective quantitative detection of OTA and ZEN in food safety control. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the possible effects and underlying molecular mechanism of Bushen‑Yizhi formula (BSYZ), a traditional Chinese medicine, on age‑related degeneration of brain physiology in senescence‑accelerated mouse prone 8 (SAMP8) mice. SAMP8 mice (age, 6 months) were administered BSYZ (1.46, 2.92 and 5.84 g/kg/day) for 30 days. Morris water maze and step‑down tests demonstrated that BSYZ significantly improved memory impairments in SAMP8 mice. In addition, BSYZ significantly enhanced the expression levels of peroxisome proliferator‑activated receptor‑γ and B‑cell lymphoma extra‑large, and downregulated the expression levels of inflammatory mediators, glial fibrillary acidic protein, cyclooxygenase‑2, nuclear factor‑κB and interleukin‑1β in the brain compared with untreated SAMP8 mice. Furthermore, BSYZ reversed disordered superoxide dismutase activity, malondialdehyde content and glutathione peroxidase activity, and ameliorated apoptosis and histological alterations. The present study indicated that BSYZ may attenuate cognitive impairment in SAMP8 mice, and modulate inflammation, oxidative stress and neuronal apoptosis. These results suggested that BSYZ may have the potential to be further developed into a therapeutic agent for protection against age‑related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

It is difficult to interpret ultrasonic signals when the echoes that are reflected from the various target features overlap. In this paper, a pulse compression technique based on a combination of Wiener filtering and autoregressive (AR) spectral extrapolation is used to process ultrasonic signals to improve their temporal resolution. The influence of the AR order and the width of the frequency window in AR spectral extrapolation are discussed in detail, and optimal parameters are obtained. The technique is then applied to measure the size of the defects in a plate and discern two adjacent defects in a block using a phased array. It is shown that the widths of the defects in the plate were measured accurately and the two adjacent defects were distinguished well by the proposed technique. [ABSTRACT FROM AUTHOR]

Dictionary learning has recently attracted a great deal of attention due to its efficacy in sparse representation based image classification task. There are two main limitations of the Sparse Representation based Classification (SRC) for applications. One is that the training data is required to be less corrupted, and the other is that each class should have sufficient training samples. To overcome these two critical issues, we propose a novel approach, namely Discriminative and Common hybrid Dictionary Learning (DCDL), for solving robust face recognition. With the priori target rank information, the DCDL is able to recover a clean discriminative dictionary by exploiting underlying low-rank structure of training data. Simultaneously, the common intra-class variation dictionary is learned to make sure that a query image can be better represented by the collaboration with image variations of other classes. Extensive experiments on representative face databases show that the proposed approach outperforms the state-of-the-art sparse representation based algorithms in dealing with non-occluded face recognition, and yields significant performance improvements in most cases of occluded face recognition. [ABSTRACT FROM AUTHOR]

Background: An impairment of the integrity of the mucosal epithelial barrier can be observed in the course of various gastrointestinal diseases. The migration and proliferation of the intestinal epithelial (IEC-6) cells are essential repair modalities to the healing of mucosal ulcers and wounds. Atractylenolide I (AT-I), one of the major bioactive components in the rhizome of Atractylodes macrocephala Koidz. (AMR), possesses multiple pharmacological activities. This study was designed to investigate the therapeutic effects and the underlying molecular mechanisms of AT-I on gastrointestinal mucosal injury.Methods: Scratch method with a gel-loading microtip was used to detect IEC-6 cell migration. The real-time cell analyzer (RTCA) system was adopted to evaluate IEC-6 cell proliferation. Intracellular polyamines content was determined using high performance liquid chromatography (HPLC). Flow cytometry was used to measure cytosolic free Ca2+ concentration ([Ca2+]c). mRNA and protein expression of TRPC1 and PLC-γ1 were determined by real-time PCR and Western blotting assay respectively.Results: Treatment of IEC-6 cells with AT-I promoted cell migration and proliferation, increased polyamines content, raised cytosolic free Ca2+ concentration ([Ca2+]c), and enhanced TRPC1 and PLC-γ1 mRNA and protein expression. Depletion of cellular polyamines by DL-a-difluoromethylornithine (DFMO, an inhibitor of polyamine synthesis) suppressed cell migration and proliferation, decreased polyamines content, and reduced [Ca2+]c, which was paralleled by a decrease in TRPC1 and PLC-γ1 mRNA and protein expression in IEC-6 cells. AT-I reversed the effects of DFMO on polyamines content, [Ca2+]c, TRPC1 and PLC-γ1 mRNA and protein expression, and restored IEC-6 cell migration and proliferation to near normal levels.Conclusion: Our data demonstrate that AT-I stimulates intestinal epithelial cell migration and proliferation via the polyamine-mediated Ca2+ signaling pathway. Therefore, AT-I may have the potential to be further developed as a promising therapeutic agent to treat diseases associated with gastrointestinal mucosal injury, such as inflammatory bowel disease and peptic ulcer. [ABSTRACT FROM AUTHOR]

This contribution reports results from the gas-phase oxidation of 4-bromo-4'-chlorobiphenyl (4,4'-BCB) in order to fathom the formation of toxic species produced during the combustion of mixed halogenated aromatics. In their own right, mixed polybrominated/polychlorinated biphenyls (PXBs) represent a new class of environmental contaminants, recently detected in food and human tissues. Gas chromatography-quadrupole mass spectrometry (GC-QMS), gas chromatography-quadrupole time of flight mass spectrometry (GC-QTOFMS), Fourier transform infrared spectroscopy (FTIR) and ion chromatography (IC) served to analyse the volatile and semi-volatile organic compounds (V/SVOCs), including mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs), and gaseous products including HBr/HCl. The selection of non-ortho substituted PXB as a model species yields a large number of halogenated compounds, including monochloro- and monobromobenzene and higher halogenated benzenes and naphthalenes and derivatives of halogenated benzenes (such as 1-chloro-4-ethynylbenzene). We also detect small amounts of chlorinated and mixed halogenated dibenzofurans. The present study provides insights into the formation of several classes of halogenated and mixed-halogenated pollutants in combustion processes involving both bromine and chlorine sources, such as those of brominated flame retardants and PVC plastics. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE) is a global zoonotic disease caused by Echinococcus granulosus, posing a great threat to human and animal health. MiRNAs are small regulatory noncoding RNA involved in the pathogenesis of parasitic diseases, possibly via exosomes. Egr-miR-71 has been identified as one of the miRNAs in the blood of CE patients, but its secretory characteristics and functions remains unclear. Herein, we studied the secretory and biological activity of exosomal egr-miR-71 and its immunoregulatory functions in sheep peripheral blood mononuclear cells (PBMCs). Our results showed that egr-miR-71 was enriched in the exosome secreted by protoscoleces with biological activity. These egr-miR-71-containing exosomes were easily internalized and then induced the dysregulation of cytokines (IL-10 and TNF-α), nitric oxide (NO) and key components (CD14 and IRF5) in the LPS/TLR4 pathway in the coincubated sheep PBMCs. Similarly, egr-miR-71 overexpression also altered the immune functions but exhibited obvious differences in regulation of the cytokines and key components, preferably inhibiting proinflammatory cytokines (IL-1α, IL-1β and TNF-α). These results demonstrate that exosomal egr-miR-71 is bioactive and capacity of immunomodulation of PBMCs, potentially being involved in immune responses during E. granulosus infection.

Recognizing the discursive nature of heritage and its crisis of representation, this paper proposes to use what we call "multi-discursive ethnography" as a methodological and writing strategy to renarrate and thereby remake heritage in contemporary China. Multi-discursive ethnography, as its name indicates, is a form of ethnography that encompasses multiple discourses of a subject matter and strives to facilitate dialogue among them. Scholars are required to conduct fieldwork and other research procedures to expose them to varied discourses, and then write up an ethnography by assembling and weaving together those discourses they find useful for representing dialogue and diversity. As a case study, we present a multi-discursive ethnography of the Heavenly Queen Palace (Tianhou Gong 天后宮) in Quzhou(衢州), Zhejiang Province, focusing chiefly on the Yueju opera (越劇) performances that many local people attend. Stories are told there, allowing us to rethink and reconstruct heritage beyond disciplinary knowledge and universalized meaning-making. This multi-discursive ethnography, we argue, problematizes globalized heritage discourses and invites a diverse and dialogical reconceptualization of a local past in the present by foregrounding vernacular voices and deep cultural discourse, especially with regard to li (禮), which is considered to be "the determinate fabric of Chinese culture, and...the language through which the culture is expressed" (Hall and Ames 1998, 269). [ABSTRACT FROM AUTHOR]