Molecular mechanism of autophagy in porcine reproductive and respiratory syndrome virus infection.

Porcine reproductive and respiratory syndrome virus (PRRSV), a significant pathogen affecting the swine industry globally, has been shown to manipulate host cell processes, including autophagy, to facilitate its replication and survival within the host. Autophagy, an intracellular degradation process crucial for maintaining cellular homeostasis, can be hijacked by viruses for their own benefit. During PRRSV infection, autophagy plays a complex role, both as a defense mechanism of the host and as a tool exploited by the virus. This review explores the current understanding of the molecular mechanisms underlying autophagy induction under PRRSV infection, its impact on virus replication, and the potential implications for viral pathogenesis and antiviral strategies. By synthesizing the latest research findings, this article aims to enhance our understanding of the intricate relationship between autophagy and PRRSV, paving the way for novel therapeutic approaches against this swine pathogen.

Bioremediation of uranium enriched coal fly ash based on microbially induced calcite precipitation.

Coal fly ash (CFA) is an essential raw material in brickmaking industry worldwide. There are some coal mines with a relatively high content of uranium (U) in the Xinjiang region of China that are yet understudied. The CFA from these coal mines poses substantial environmental risks due to the concentrated uranium amount after coal burning. In this paper, we demonstrated a calcifying ureolytic bacterium Halomonas sp. SBC20 for its biocementation of U in CFA based on microbially induced calcite precipitation (MICP). Rectangle-shaped CFA bricks were made from CFA using bacterial cells, and an electric testing machine tested their compressive strength. U distribution pattern and immobility against rainfall runoff were carefully examined by a five-stage U sequential extraction method and a leaching column test. The microstructural changes in CFA bricks were characterized by FTIR and SEM-EDS methods. The results showed that the compressive strength of CFA bricks after being cultivated by bacterial cells increased considerably compared to control specimens. U mobility was significantly decreased in the exchangeable fraction, while the U content was markedly increased in the carbonate-bound fraction after biocementation. Much less U was released in the leaching column test after the treatment with bacterial cells. The FTIR and SEM-EDX methods confirmed the formation of carbonate precipitates and the incorporation of U into the calcite surfaces, obstructing the release of U into the surrounding environments. The technology provides an effective and economical treatment of U-contaminated CFA, which comes from coal mines with high uranium content in the Xinjiang region, even globally.

Rational Design of Human Hair Keratin-Driven Proteins for Hair Growth Promotion.

Keratins, the most abundant proteins in human hair, are excellent hair nutrients for growth. However, the complex components of keratin extract hinder their mechanism investigation, and the pure recombinant keratin with poor solubility limited its hair growth promotion efficiency. Here, the water-soluble recombinant keratins (RKs) of K31 and K81 are rationally designed through QTY Code methodology, which are then used to fabricate the microneedles to study the effect of keratin on hair growth. Interestingly, it is discovered that more than 40% of the hair follicles (HFs) in the RK81QTY group entered the anagen on day 12 and the diameter of new hair is 15.10 ± 2.45 µm, which significantly promoted growth and development of HFs and improved new hair quality compared to RK31QTY. Water-soluble RKs significantly enhanced HFs activity and de novo regeneration of robust hairs compared to extract and minoxidil by upregulating the PI3K/AKT/Nf-κB signaling axis. These findings highlight the potential of designing solubilized recombinant keratins with distinct properties to improve therapeutical effects and open new avenues to designing keratin-based proteins.

From sutureless to standard: a comprehensive analysis of conversion rates in laparoscopic partial nephrectomy.

OBJECTIVE: To assess the rate at which sutureless partial nephrectomy (SLPN) transitions to standard partial nephrectomy (SPN), focusing on preoperative factors that might prompt such conversions. PATIENTS AND METHODS: In this retrospective study, we analyzed the efficacy of SLPN performed on adults at our institution from 2016 to 2023. The subjects were patients diagnosed with localized solid renal tumors. The primary technique employed was resection with scissors and argon beam coagulation for hemostasis, with suturing techniques used only when necessary. Predictive factors necessitating conversion to SPN were identified, and the associations among multiple variables were explored using various statistical analysis methods, including logistic regression, to identify key preoperative predictive factors. RESULTS: Our institution performed 353 SLPN, with 21 cases (5.9%) necessitating conversion to SPN. The conversion rates for the Laparoscopic Partial Nephrectomy (LPN) subgroup and the Robotic-assist Partial Nephrectomy (RPN) subgroup were 7.9% (17/215) and 2.9% (4/138), respectively, nearing statistical significance (P = .066). Significant differences were observed between the conversion group and the no conversion group in terms of preoperative estimated Glomerular Filtration Rate (eGFR), age at surgery, tumor size, and exophytic/endophytic characteristics. Multivariate analysis identified age at surgery, preoperative eGFR, radiological tumor size, and tumor exophytic/endophytic nature as significant predictors for conversion to SPN. CONCLUSION: This investigation highlights the efficacy and feasibility of SLPN while identifying critical factors influencing the necessity for conversion to SPN. The identified predictors, including younger surgical age, superior preoperative eGFR, and specific tumor characteristics, provide valuable insights for refining surgical strategies.

Evaluation of the prognosis in patients with small-cell lung cancer treated by chemotherapy using tumor shrinkage rate-based radiomics.

BACKGROUND: Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. METHODS: We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan-Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. RESULTS: The TSR cutoff was identified to be - 6.6%. Median PFS and OS were longer in the group with a TSR < -6.6% than in the group with a TSR ≥ - 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < - 6.6% than when it was > - 6.6%. Brain metastasis-free survival was better in the group with a TSR < - 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS. CONCLUSIONS: The TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.

The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan.

The drugs extending healthspan in clinic have always been searched. Nitazoxanide is an FDA-approved clinical antiprotozoal drug. Nitazoxanide is rapidly metabolized to tizoxanide after absorption in vivo. Our previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK, oral nitazoxanide protects against experimental hyperlipidemia, hepatic steatosis, and atherosclerosis. Here, we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 pathway. Additionally, both nitazoxanide and tizoxanide improve high glucose-induced shortening of C. elegans lifespan. Nitazoxanide has been a clinical drug with a good safety profile, we suggest that it is a novel anti-aging drug.

Iodine status and knowledge among pregnant and lactating women in Large City in Northern China after nearly 30 years of the universal salt iodization.

BACKGROUND: With the implementation of the universal salt iodization, the iodine nutrition for children and adults has been appropriate, but pregnant women are still at risk of iodine deficiency. It is of great public health significance to explore the iodine status and knowledge, and influence factors and the appropriate health education methods among pregnant and lactating women. METHODS: From January 2022 to December 2023, at least 50 pregnant women and 50 lactating women were randomly selected from the resident population annually in 16 districts of Tianjin, North China. A total of 1671 pregnant women and 1658 lactating women were recruited. All participants' households salt and random urine samples were collected. A questionnaire was conducted to collect data on iodine related knowledge and behaviors as well as needs of health education from all participants. Logistic regression models were constructed to analyze the factors affecting the iodine related knowledge level. We used the Rasch model and the quadrantal graph to analyze the participants' knowledge level on different iodine-related questions and their needs for health education. RESULTS: The median urine iodine concentration (UIC) of pregnant and lactating women in Tianjin were 152.40 µg/L and 124.60 µg/L. In some districts, the median UIC of pregnant and lactating women below the appropriate range. The iodized salt coverage rate of pregnant and lactating women in Tianjin was 76.12% and 77.40%, respectively. In pregnant and lactating women who did not actively supplement with iodine, the median UIC in those who consumed non-iodized salt were significantly lower than that in those who consumed iodized salt (139.26 µg/L and 154.40 µg/L, P = 0.044; 94.60 µg/L and 123.80 µg/L, P < 0.001). Compared with the low knowledge score group, pregnant women in the high knowledge score group had a higher proportion of iodized salt consumption (71.25% and 78.05%, P = 0.003), and pregnant and lactating women in the high knowledge score group had a higher proportion of actively supplement iodine (44.61% and 55.34%, P < 0.001; 39.26% and 49.78%, P < 0.001). Health education may be the main factor affecting the iodine related knowledge scores for pregnant and lactating women, with adjusted odds ratios (OR) and 95% confidence intervals (CI) of 2.89 (2.30, 3.62) and 2.46 (1.97, 3.07), respectively. Pregnant and lactating women are most expected to acquire knowledge through healthcare professionals (72.11%) and wechat/website (74.91%), respectively. CONCLUSIONS: Pregnant and lactating women in some areas of Tianjin are at risk of iodine deficiency. Iodized salt consumption is an important way to ensure iodine nutrition of the population, and the lack of iodine related knowledge is an important factor affecting the consumption of iodized salt. Health education in different ways can be carried out for different people to improve the acceptance and efficiency of health education.

Preparation and Characterization of Silica-Coated Sodium Alginate Hydrogel Beads and the Delivery of Curcumin.

In this study, to address the defects of sodium alginate (SA), such as its susceptibility to disintegration, silica was coated on the outer layer of sodium alginate hydrogel beads in order to improve its swelling and slow-release properties. Tetraethyl orthosilicate (TEOS) was used as the hydrolyzed precursor, and the solution of silica precursor was prepared by sol-gel reaction under acidic conditions. Then SA-silica hydrogel beads prepared by ionic crosslinking method were immersed into the SiO2 precursor solution to prepare SA-silica hydrogel beads. The chemical structure and morphology of the hydrogel beads were characterized by XRD, FTIR, and SEM, and the results showed that the surface of SA-silica beads was successfully encapsulated with the outer layer of SiO2, and the surface was smooth and dense. The swelling experiments showed that the swelling performance effectively decreased with the increase of TEOS molar concentration, and the maximum swelling ratio of the hydrogel beads decreased from 41.07 to 14.3, and the time to reach the maximum swelling ratio was prolonged from 4 h to 8 h. The sustained-release experiments showed that the SA-silica hydrogel beads possessed a good pH sensitivity, and the time of sustained-release was significantly prolonged in vitro. Hemolysis and cytotoxicity experiments showed that the SA-silica hydrogel beads were biocompatible when the TEOS molar concentration was lower than 0.375 M. The SA-silica-2 hydrogel beads had good biocompatibility, swelling properties, and slow-release properties at the same time.

Unveiling the Correlation Between the Membrane Assembly of P-gp and Drug Resistance in Multiple Myeloma Using Super-Resolution Fluorescence Imaging.

Drug resistance in multiple myeloma (MM) poses a significant challenge to treatment efficacy, primarily attributed to P-glycoprotein (P-gp) dysfunction. This study delves into the elusive spatial organization of P-gp, aiming to enhance our understanding of its role in MM drug resistance by exploring the intricate relationship between molecular function and spatial arrangement. Employing super-resolution imaging of P-gp with the inhibitor probe Tariquidar-TAMR labeling on MM cell membranes, the research uncovered a more pronounced clustering distribution of P-gp in drug-resistant cells (MM1R) compared to drug-sensitive counterparts (MM1S). Further exploration revealed the clustering distribution of P-gp was heightened as cellular drug resistance increased in hypoxic condition, directly emphasizing the strong correlation between P-gp cluster morphology and drug resistance. Additionally, stable P-gp cluster formation was influenced by cross-linking of membrane carbohydrates, and disrupting these glycoprotein clusters could reduce cellular drug resistance, suggesting that altering distribution patterns of P-gp can modulate drug responsiveness. Finally, dexamethasone (Dex) treatment was revealed to enhance P-gp clustering distribution, particularly in MM1S cells, indicating that change degree in P-gp distribution correlate with the modifiable space of cellular drug responsiveness. This study provides insights into the correlation between P-gp assembly and cellular drug responsiveness, deepening our understanding of functional changes in MM drug resistance and offering valuable perspectives for overcoming this challenge.

The heat shock protein DNAJB8 inhibits pseudorabies virus replication by autophagy.

Pseudorabies virus (PRV) effectively utilizes numerous host proteins and pathways to establish a successful infection. Consequently, it becomes imperative to investigate novel host factors implicated in viral infections to gain a deeper understanding of PRV pathogenesis. In this study, we reveal that the host heat shock protein, DNAJB8, functions as a negative regulator in PRV replication. Our findings indicated that both mRNA and protein levels of DNAJB8 were downregulated in cells infected with PRV. Further analysis demonstrated that overexpressing DNAJB8 suppressed PRV replication, whereas its knockdown enhanced viral replication. From a mechanistic perspective, DNAJB8 promoted cellular autophagy, subsequently impeding viral replication. Additionally, we discovered that the transcription factor SOX30 regulated DNAJB8 expression, thereby influencing viral replication. Collectively, these findings enhance our comprehension of the roles played by DNAJB8 and SOX30 in viral replication, broadening our knowledge of virus-host interactions.

Large cells suppress the reproduction of Varroa destructor.

BACKGROUND: The parasitic mite, Varroa destructor has posed a threat to the health and survival of European honey bees, Apis mellifera worldwide. There is a prevailing belief that small comb cells could provide a management tool against Varroa mites. However, the hypothesis that smaller cells can impede Varroa reproduction has not been fully tested. Here, we tested this hypothesis under laboratory conditions by using two distinct Varroa in vitro rearing systems: one involved gelatin capsules of different sizes, specifically size 00 (0.95 mL) versus size 1 (0.48 mL), and the second consisted of brood comb cells drawn on 3D printed foundations with varying cell sizes, ranging from 5.0 mm to 7.0 mm at 0.5 mm intervals. RESULTS: The results showed that mother mites in size 00 cells had significantly lower fecundity and fertility compared to those in size 1 cells. Interestingly, the reproductive suppression in larger cells could be reversed by adding an extra worker larva. Similarly, gonopore size of mother mites was smaller in size 00 cells, but restored with another host larva. Furthermore, both the fecundity and fertility of mother mites decreased linearly with the size of brood comb cells. CONCLUSIONS: Our results suggest that the reproduction of V. destructor is hindered by larger cells, possibly because larger brood cells disperse or weaken host volatile chemical cues that are crucial for Varroa reproduction. The insights derived from this study are expected to hold significant implications for the implementation of Varroa management programs. © 2024 Society of Chemical Industry.

Preparation of sodium alginate modified silver-metal organic framework and application in citric acid/PVA antimicrobial packaging.

Silver-metal organic framework (Ag@MOF) has exhibited outstanding antimicrobial activity in antimicrobial applications, and reducing the biotoxicity associated with silver has become a research priority. In this study, Ag@MOF was initially modified with sodium alginate (SA) to form SA-Ag@MOF. The results showed that SA could control the release of Ag+, reducing the release by about 8% at 24 h, and the biotoxicity was significantly reduced. Finally, SA-Ag@MOF was applied as an antimicrobial agent in citric acid-modified PVA film to develop a novel composite antimicrobial film. When added at 2 MIC, the CA3-M2 film can effectively inhibit the growth of E. coli and S. aureus, and the inhibition rate has reached 98%. For white radish packaging applications, CA3-M2 film inhibited the growth of surface microorganisms, while ensuring moisture and tissue hardness to extend shelf-life up to 7 days. Overall, the strategy conceived here can be a theoretical basis for novel antimicrobial packaging.

Chemometric analysis illuminates the relationship among browning, polyphenol degradation, Maillard reaction and flavor variation of 5 jujube fruits during air-impingement jet drying.

This study was designed to reveal the relationship among browning, polyphenol degradation, Maillard reaction (MR) and flavor variation in jujube fruit (JF) during air-impingement jet drying (AIJD). Five kinds of JFs were dried by AIJD at 60 °C and vacuum freeze drying. Colorimeter and chemometric analysis found that AIJD induced color changes of JF pulp and peel. AIJD also reduced the total polyphenols content and total flavonoids levels in JF. The Fe3+ reducing capacity and 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulphonate) cationic radical scavenging capacity of JF were reduced by 31.6% and 8.2%, respectively. Seven polyphenols were identified in JF, and epicatechin was found related to change of JF pulp color by sparse partial least square (sPLS). sPLS revealed that 3-deoxy glucosone, N-ε-carboxymethyl-l-lysine and 5-hydroxymethylfurfural associated with JF color. sPLS found that MR generated 3-methyl-butanoic acid and cyclobutanone during AIJD of JF. Chemometrics is an effective tool to disclose mechanism of color changes in food.

[Retracted] MicroRNA­329­3p targets MAPK1 to suppress cell proliferation, migration and invasion in cervical cancer.

Following the publication of the above article, a concerned reader drew to the Editor's attention that certain of the Transwell cell migration and invasion assay data featured in Figs. 5C and 6C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published elsewhere prior to the submission of this paper to Oncology Reports, or were submitted for consideration for publication at around the same time. In view of the fact that certain of these data had already apparently been published prior to the submission of this article for publication, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 37: 2743­2750, 2017; DOI: 10.3892/or.2017.5555].

Extraction and Isolation of Two Polysaccharides from Chloranthus japonicus Sieb. and Evaluation of Their Anti-Gastric Cancer Activities.

Two unreported heteropolysaccharides, denoted as YCJP-1 and YCJP-2, were isolated from the herbs of Chloranthus japonicus. YCJP-1 was a heteropolysaccharide composed of glucose, galactose, arabinose, mannose, rhamnose, and a minor proportion of uronic acids, with the molecular weight mainly distributed in the 74,475-228,443 Da range. YCJP-2 was mainly composed of glucose, mannose, and galactose, with the molecular weights ranging from 848 to 5810 Da. To further evaluate the anti-gastric cancer effects of C. japonicus, the inhibitory effects of the crude polysaccharide (YCJP) and the purified polysaccharides (YCJP-1 and YCJP-2) were determined using a CCK-8 assay and colon-forming assay on MGC-803 and AGS gastric cancer cell lines. Our results showed that YCJP, YCJP-1, and YCJP-2 possess prominent inhibitory effects on the proliferation of MGC-803 and AGS cells, and the AGS cell was more sensitive to YCJP, YCJP-1, and YCJP-2. Moreover, YCJP-2 demonstrated superior anti-gastric cancer effects compared to YCJP-1. This could potentially be attributed to YCJP-2's higher glucose content and narrower molecular weight distribution.

Image recognition technology provides insights into relationships between anthocyanin degradation and color variation during jet drying of black carrot.

To identify interesting relationships between anthocyanin degradation and color variation during food processing, black carrot slice (BCS) was dried by air-impingement jet drying (AIJD) and hot air drying (HAD). AIJD was a better technology for drying BCS than HAD. Results of colorimeter determination showed that the color of BCS was significantly changed during AIJD at 50, 60 and 70 °C. UHPLC-QqQ-MS/MS analysis found that AIJD-induced degradations of main BCS anthocyanins, cyanidin-3-xylosyl(feruloylglucosyl)galactoside and cyanidin-3-xylosyl(sinapoylglucosyl)galactoside, belonged to non-spontaneous endothermic reactions, which followed the 0.5- and 1-order kinetic equations, respectively. Anthocyanin content and colors obtained from colorimeter presented strong positive correlation, particularly the a* and chroma values. We further developed a Python script based on image recognition technology to visualize the correlation matrixes between the anthocyanin contents and colors of BSC images. The plots revealed that strong positive correlations between anthocyanins and colors primarily concentrated in the sample's periphery following a concentric pattern.

A novel long non-coding RNA LINC00524 facilitates invasion and metastasis through interaction with TDP43 in breast cancer.

Breast cancer (BC) remains a significant health concern worldwide, with metastasis being a primary contributor to patient mortality. While advances in understanding the disease's progression continue, the underlying mechanisms, particularly the roles of long non-coding RNAs (lncRNAs), are not fully deciphered. In this study, we examined the influence of the lncRNA LINC00524 on BC invasion and metastasis. Through meticulous analyses of TCGA and GEO data sets, we observed a conspicuous elevation of LINC00524 expression in BC tissues. This increased expression correlated strongly with a poorer prognosis for BC patients. A detailed Gene Ontology analysis suggested that LINC00524 likely exerts its effects through RNA-binding proteins (RBPs) mechanisms. Experimentally, LINC00524 was demonstrated to amplify BC cell migration, invasion and proliferation in vitro. Additionally, in vivo tests showed its potent role in promoting BC cell growth and metastasis. A pivotal discovery was LINC00524's interaction with TDP43, which leads to the stabilization of TDP43 protein expression, an element associated with unfavourable BC outcomes. In essence, our comprehensive study illuminates how LINC00524 accelerates BC invasion and metastasis by binding to TDP43, presenting potential avenues for therapeutic interventions.

A preliminary metabolomics study of the database for biological samples of schizophrenia among Chinese ethnic minorities.

BACKGROUND: Schizophrenia (SCZ) is a profound mental disorder with a multifactorial etiology, including genetics, environmental factors, and demographic influences such as ethnicity and geography. Among these, the studies of SCZ also shows racial and regional differences. METHODS: We first established a database of biological samples for SCZ in China's ethnic minorities, followed by a serum metabolomic analysis of SCZ patients from various ethnic groups within the same region using the LC-HRMS platform. RESULTS: Analysis identified 47 metabolites associated with SCZ, with 46 showing significant differences between Miao and Han SCZ patients. These metabolites, primarily fatty acids, amino acids, benzene, and derivatives, are involved in fatty acid metabolism pathways. Notably, L-Carnitine, L-Cystine, Aspartylphenylalanine, and Methionine sulfoxide demonstrated greater diagnostic efficacy in Miao SCZ patients compared to Han SCZ patients. CONCLUSION: Preliminary findings suggest that there are differences in metabolic levels among SCZ patients of different ethnicities in the same region, offering insights for developing objective diagnostic or therapeutic monitoring strategies that incorporate ethnic considerations of SCZ.

Evaluating the adoption of irrigation technology in a well-irrigated winter wheat－summer maize cropping system.

Determining suitable irrigation technology is of paramount for promoting water-saving agriculture, particularly for winter wheat-summer maize rotation system in well-irrigated regions. To optimize and assess the efficacy of various irrigation technologies (specifically, semi-fixed sprinkler irrigation, walking sprinkler, semi-automatic buried telescopic sprinkler irrigation, thin-soft spray tape irrigation, drip irrigation, self-driven winch sprinkler and manually moving spray gun irrigation, marked as A, B, C, D, E, F and G) applied in south central North China Plain, we first conducted an economic analysis for the winter wheat-summer maize rotation. Subsequently, employing a comprehensive set of 20 indicators spanning economic, societal, technological, ecological, and resource aspects, we employed a TOPSIS model with integrative weighting approach using "AHP + Entropy". We also employed principal component analysis and the Sankey diagram method to explore characteristics of different irrigation techniques and indexes. Irrigation mode E, conserving energy by 63.19% compared to mode B and offering labor savings five times greater than the mode D. The highest economic benefit for the rotation system was observed with the mode C, resulting in a 25.26% increase compared to the mode G. The top three irrigation modes based on scores were D, G, and E, with scores of 0.532, 0.490, and 0.474, respectively. The Sankey diagram revealed distinct preferences among different agricultural entities for specific irrigation modes. For specific stakeholders, we recommend irrigation modes D, G, F, and B for small farmers, large and specialized family businesses, family farms, and farmer cooperatives, respectively. In conclusion, our findings provide valuable scientific support and recommendations for the practical application of irrigation technology in agricultural production.