Application of surface-modified functional packaging in food storage: A comprehensive review.

Innovations in food packaging systems could meet the evolving needs of the market; emerging concepts of non-migrating technologies reduce the negative migration of preservatives from packaging materials, extend shelf life, and improve food quality and safety. Non-migratory packaging activates the surface of inert materials through pretreatment to generate different active groups. The preservative is covalently grafted with the resin of the pretreated packaging substrate through the graft polymerization of the monomer and the coupling reaction of the polymer chain. The covalent link not only provides the required surface properties of the material for a long time but also retains the inherent properties of the polymer. This technique is applied to the processing for durable, stable, and easily controllable packaging widely. This article reviews the principles of various techniques for packaging materials, surface graft modification, and performance characterization of materials after grafting modification. Potential applications in the food industry and future research trends are also discussed.

Nitrogen addition changed soil fungal community structure and increased the biomass of functional fungi in Korean pine plantations in temperate northeast China.

Nitrogen (N) deposition is a global environmental issue that can have significant impacts on the community structure and function in ecosystems. Fungi play a key role in soil biogeochemical cycles and their community structures are tightly linked to the health and productivity of forest ecosystems. Based on high-throughput sequencing and ergosterol extraction, we examined the changes in community structure, composition, and biomass of soil ectomycorrhizal (ECM) and saprophytic (SAP) fungi in 0-10 cm soil layer after 8 years of continuous N addition and their driving factors in a temperate Korean pine plantation in northeast China. Our results showed that N addition increased fungal community richness, with the highest richness and Chao1 index under the low N treatment (LN: 20 kg N ha-1 yr-1). Based on the FUN Guild database, we found that the relative abundance of ECM and SAP fungi increased first and then decreased with increasing N deposition concentration. The molecular ecological network analysis showed that the interaction between ECM and SAP fungi was enhanced by N addition, and the interaction was mainly positive in the ECM fungal network. N addition increased fungal biomass, and the total fungal biomass (TFB) was the highest under the MN treatment (6.05 ±â€¯0.3 mg g-1). Overall, we concluded that N addition changed soil biochemical parameters, increased fungal activity, and enhanced functional fungal interactions in the Korean pine plantation over an 8-year simulated N addition. We need to consider the effects of complex soil conditions on soil fungi and emphasize the importance of regulating soil fungal community structure and biomass for managing forest ecosystems. These findings could deepen our understanding of the effects of increased N deposition on soil fungi in temperate forests in northern China, which can provide the theoretical basis for reducing the effects of increased N deposition on forest soil.

Effect of the coloring liquid shade and dipping time on the color, transparency, and flexural strength of monolithic zirconia.

STATEMENT OF PROBLEM: The impact of different coloring liquid shades and dipping times on the color, transparency, and flexural strength of monolithic zirconia ceramics is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effects of different coloring liquid shades (A2, 3M2, and 5M2) and dipping times (no dipping, 30 seconds, 60 seconds, and 90 seconds) on the color difference (ΔE00), relative translucency parameter (ΔRTP00), and 3-point flexural strength (σ) of monolithic zirconia ceramics. MATERIAL AND METHODS: Yttria-stabilized zirconia (3Y-TZP, 3 mol%) was cut into Ø16×1.2-mm plates (n=10) and 25×4×1.2-mm bars (n=15), which were colored using 3 shades of coloring liquid at 4 dipping times. Color coordinates were measured on a gray background by using a digital spectrophotometer with an integrating sphere attachment. The color and translucency differences were evaluated using 50:50% perceptibility (PT00 and TPT00) and acceptability (AT00 and TAT00) thresholds. The 3-point flexural strengths of the bar-shaped specimens were measured using a universal testing machine and analyzed using the Weibull distribution to calculate the Weibull modulus (m) and characteristic fracture strength (σ0). The data were analyzed with the 2-way ANOVA, Kruskal-Wallis, and LSD post hoc tests (α=.05). RESULTS: Both shade and dipping time significantly affected the color and translucency of monolithic zirconia (P<.001). The ΔE00 was above the PT00 for all groups, with only 3M2-90 and A2-60 being below the AT00. The main cause of color differences was the difference in lightness. Only A2 showed ΔRTP00 below the TPT00 (A2-30 (ΔRTP00=0.26), A2-60 (ΔRTP00=0.29), and A2-90 (ΔRTP00=0.46)). All experimental groups showed translucency differences below TAT00. In addition, only the dipping time had a significant effect on the flexural strength of zirconia (P<.001). CONCLUSIONS: The optical properties of monolithic zirconia ceramics were affected by the shade and dipping time of the coloring liquid. The mismatch in lightness was the main reason for the color difference. The dipping time affects the flexural strength of monolithic zirconia, whereas the shade of the coloring liquid did not seem to influence flexural strength.

Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

[Le miR-224-5p régulé sert de biomarqueur pour l'insuffisance hépatique aiguë pédiatrique et régule l'inflammation en modulant ZBTB20]. / Upregulated miR-224-5p served as a biomarker for pediatric acute liver failure and regulate inflammation by modulating ZBTB20.

Pediatric acute liver failure (PALF) is a severe liver dysfunction with complex pathological mechanisms and rapid development. MiRNAs have been identified as promising biomarkers for human disease screening and monitoring. This study focused on evaluating the clinical significance of miR-224-5p in PALF and revealing its potential molecular mechanism in regulating liver cell injury. This study enrolled 103 children with PALF and 55 healthy children without liver diseases. Serum miR-224-5p levels were compared between the two groups, and their clinical significance was estimated by analyzing the correlation with clinicopathological features and outcomes of PALF children. In vitro, a normal liver cell was treated with lipopolysaccharide (LPS), and cell growth and inflammation were assessed by CCK8 and ELISA assay. Upregulated miR-224-5p in PALF showed significance in screening PALF children from healthy children with the sensitivity and specificity of 78.64% and 84.47%, respectively. Increasing serum miR-224-5p in PALF children was closely associated with increasing prothrombin time, alanine transaminase, international normalized ratio, total bilirubin, ammonia, and aspartic transaminase and decreasing albumin of PALF children. MiR-224-5p was also identified as a risk factor for adverse outcomes in children with PALF. In LPS-treated liver cells, miR-224-5p could negatively regulate ZBTB20, and silencing miR-224-5p could alleviate the inhibited cell growth and promoted inflammation by LPS, which was reversed by ZBTB20 knockdown. Increasing miR-224-5p distinguished PALF children, predict severe disease development and risk of adverse prognosis. miR-224-5p also reguled LPS-induced liver cell injury via negatively regulating ZBTB20.

Modeling assessment of air pollution control measures and COVID-19 pandemic on air quality improvements over Greater Bay Area of China.

A remarkable progress has been made toward the air quality improvements over the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China from 2017 to 2020. In this study, for the first time, the emission reductions of regional control measures together with the COVID-19 pandemic were considered simultaneously into the development of the GBA's emission inventories for the years of 2017 and 2020. Based on these collective emission inventories, the impacts of control measures, meteorological variations together with temporary COVID-19 lockdowns on the five major air quality index pollutants (SO2, NO2, PM2.5, PM10, and O3, excluding CO) were evaluated using the WRF-CMAQ and SMAT-CE model attainment assessment tool over the GBA region. Our results revealed that control measures in the Pearl River Delta (PRD) region affected significantly the GBA, resulting in pollutant reductions ranging from 48 % to 64 %. In contrast, control measures in Hong Kong and Macao contributed to pollutant reductions up to 10 %. In PRD emission sectors, stationary combustion, on-road, industrial processes and dust sectors stand out as the primary contributors to overall air quality improvements. Moreover, the COVID-19 pandemic during period I (Jan 23-Feb 23) led to a reduction of NO2 concentration by 7.4 %, resulting in a negative contribution (disbenefit) for O3 with an increase by 2.4 %. Our findings highlight the significance of PRD control measures for the air quality improvements over the GBA, emphasizing the necessity of implementing more refined and feasible manageable joint prevention and control policies.

A mechanism for the treatment of cardiovascular and renal disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. CVD and kidney disease are closely related, with kidney injury increasing CVD mortality. The pathogenesis of cardiovascular and renal diseases involves complex and diverse interactions between multiple extracellular and intracellular signaling molecules, among which transient receptor potential vanilloid 1 (TRPV1)/ transient receptor potential ankyrin 1(TRPA1) channels have received increasing attention. TRPV1 belongs to the vanilloid receptor subtype family of transient receptor potential (TRP) ion channels, and TRPA1 belongs to the TRP channel superfamily. TRPV1/TRPA1 are jointly involved in the management of cardiovascular and renal diseases, and play important roles in regulating vascular tension, promoting angiogenesis, anti-fibrosis, anti-inflammation, and anti-oxidation. The mechanism of TRPV1 / TRPA1 is mainly related to regulation of intracellular calcium influx and release of nitric oxide (NO) and calcitonin gene-related peptide (CGRP). Therefore, this study takes TRPV1 / TRPA1 channel as the research object, analyzes and summarizes the process and mechanism of TRPV1 / TRPA1 affecting cardiovascular and renal diseases, and lays a foundation for the treatment of cardio-renal diseases.

Validation of the revised electronic version of RUCAM for diagnosis of DILI in Chinese patients.

BACKGROUND AIMS: The Revised Electronic Causality Assessment Method (RECAM), a computerized update of the Roussel Uclaf Causality Assessment Methodology (RUCAM), was recently proposed. In this study, we validated and compared the utility of the RECAM and RUCAM in Chinese patients with a single conventional or herbal agent-induced liver injury. METHODS: In this retrospective multicenter cohort of well-established DILI and non-DILI patients from 5 centers in China, the diagnostic performance of the RUCAM and RECAM was compared by AUC analysis. The consistency was evaluated by weighted kappa. The major causes of discrepancy were explored. RESULTS: A total of 481 DILI and 100 non-DILI patients were included. In total, 62.6% of the DILI cases were induced by conventional agents, and 37.4% were induced by herbs. The RECAM had relatively higher AUC than RUCAM for overall [0.947 (0.926-0.964) vs. 0.867 (0.836-0.893), p=0.0016], conventional agents [0.923 (0.890-0.949) vs. 0.819 (0.775-0.858), p=0.0185], and herbs [0.972 (0.941-0.989) vs.0.911 (0.866-0.944), p=0.0199]. Latency, scores associated with hepatitis B, and hepatotoxicity information of the insulting drugs were the 3 main causes for the inconsistency between RECAM and RUCAM scores. CONCLUSIONS: The RECAM had relatively better diagnostic performance than RUCAM, with a higher AUC for Chinese DILI patients. Timely updates of the LiverTox category and refinement of serum markers to exclude hepatitis B activity would further improve the applicability of RECAM in areas where the use of herbs and resolution of past HBV infections are common.

Genome-Wide Identification and Drought Stress Response Pattern of the NF-Y Gene Family in Cymbidium sinense.

Cymbidium sinense, a type of orchid plant, is more drought-resistant and ornamental than other terrestrial orchids. Research has shown that many members of the NUCLEAR FACTOR Y (NF-Y) transcription factor family are responsive to plant growth, development, and abiotic stress. However, the mechanism of the NF-Y gene family's response to abiotic stress in orchids has not yet been reported. In this study, phylogenetic analysis allowed for 27 CsNF-Y genes to be identified (5 CsNF-YAs, 9 CsNF-YBs, and 13 CsNF-YC subunits), and the CsNF-Ys were homologous to those in Arabidopsis and Oryza. Protein structure analysis revealed that different subfamilies contained different motifs, but all of them contained Motif 2. Secondary and tertiary protein structure analysis indicated that the CsNF-YB and CsNF-YC subfamilies had a high content of alpha helix structures. Cis-element analysis showed that elements related to drought stress were mainly concentrated in the CsNF-YB and CsNF-YC subfamilies, with CsNF-YB3 and CsNF-YC12 having the highest content. The results of a transcriptome analysis showed that there was a trend of downregulation of almost all CsNF-Ys in leaves under drought stress, while in roots, most members of the CsNF-YB subfamily showed a trend of upregulation. Additionally, seven genes were selected for real-time reverse transcription quantitative PCR (qRT-PCR) experiments. The results were generally consistent with those of the transcriptome analysis. The regulatory roles of CsNF-YB 1, 2, and 4 were particularly evident in the roots. The findings of our study may make a great contribution to the understanding of the role of CsNF-Ys in stress-related metabolic processes.

Imatinib@glycymicelles entrapped in hydrogel: preparation, characterization, and therapeutic effect on corneal alkali burn in mice.

Imatinib (IMB) is a type of tyrosine kinase inhibitor with great application potential for inhibiting corneal neovascularization (CNV), but its poor water solubility limits its application in eye disease treatment. In this study, novel IMB@glycymicelles entrapped in hydrogel (called IMB@glycymicelle-hydrogel) were prepared, characterized, and evaluated for their therapeutic effects on corneal alkali burn in mice. Imatinib could be successfully loaded in glycymicelles using glycyrrhizin as a nanocarrier with an optimized weight ratio of IMB:nanocarrier. The apparent solubility of IMB was significantly improved from 61.69 ± 5.55 µg/mL to bare IMB to 359,967.62 ± 20,059.42 µg/mL to IMB@glycymicelles. Then, the IMB@glycymicelles were entrapped in hydrogel fabricated with hydroxypropyl methylcellulose and sodium hyaluronate (HA) to prolong retention time on the ocular surface. Rabbit eye tolerance tests showed that IMB@glycymicelle-hydrogel possessed good ocular safety profiles. In a mouse model of corneal alkali burns, the topical administration of IMB@glycymicelle-hydrogel showed strong efficacy by prompting corneal wound healing, recovering corneal sensitivity, relieving corneal opacities, and inhibiting CNV, and these efficacy evaluation parameters were better than those of the positive drug HA. Overall, these results demonstrated that IMB@glycymicelle-hydrogel may be a promising candidate for the effective treatment of alkali ocular damage.

24Model-based comparative analysis of two catastrophic hazardous chemical pipeline accidents.

Objectives. This study conducted a comparative analysis of two catastrophic pipeline accidents in China in order to identify some common mistakes and lessons learned to prevent similar accidents. Methods. The 24Model was used in this study, which provides a universal pathway for accident analysis from the individual level to the organizational level. Results. There were similarities between the two cases in the aspects of the occurrence, development, emergency and causation at different levels: both were caused by leaks of pipelines and evolved into multiple explosions during emergency response; both leaks were caused by the corrosion of pipelines in the confined space of a damp or salt-spray environment; both were classified as 'responsibility accidents', and unsafe acts, such as the failure to identify hidden hazards of pipelines that were the direct cause of accidents, reflected the shortcomings of individual safety habitual behaviour in terms of knowledge, awareness, habits and psychology; weaknesses in the organizational management mainly concerned hazard identification, pipeline maintenance, emergency disposal, etc.; and there is not a good safety climate within the organization. Conclusions. Organizations should develop a closed-loop management system and strengthen the construction of safety culture, and the government should supervise the implementation of procedures.

Upconversion dual-photosensitizer-expressing bacteria for near-infrared monochromatically excitable synergistic phototherapy.

Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe the development of upconversion dual-photosensitizer-expressing bacteria (UDPB) for near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering and surface modification, in which bacteria are encoded to simultaneously express photothermal melanin and phototoxic KillerRed protein and the surface primary amino groups are derived to free thiols for biorthogonal conjugation of upconversion nanoparticles. UDPB exhibit a near-infrared monochromatic irradiation-mediated dual-activation characteristic as the photothermal conversion of melanin can be initiated directly, while the photodynamic effect of KillerRed can be stimulated indirectly by upconverted visible light emission. UDPB also show living features to colonize hypoxic lesion sites and inhibit pathogens via bacterial community competition. In two murine models of solid tumor and skin wound infection, UDPB separately induce robust antitumor response and a rapid wound healing effect.

Defective prelamin A processing promotes unconventional necroptosis driven by nuclear RIPK1.

Defects in the prelamin A processing enzyme caused by loss-of-function mutations in the ZMPSTE24 gene are responsible for a spectrum of progeroid disorders characterized by the accumulation of farnesylated prelamin A. Here we report that defective prelamin A processing triggers nuclear RIPK1-dependent signalling that leads to necroptosis and inflammation. We show that accumulated prelamin A recruits RIPK1 to the nucleus to facilitate its activation upon tumour necrosis factor stimulation in ZMPSTE24-deficient cells. Kinase-activated RIPK1 then promotes RIPK3-mediated MLKL activation in the nucleus, leading to nuclear envelope disruption and necroptosis. This signalling relies on prelamin A farnesylation, which anchors prelamin A to nuclear envelope to serve as a nucleation platform for necroptosis. Genetic inactivation of necroptosis ameliorates the progeroid phenotypes in Zmpste24-/- mice. Our findings identify an unconventional nuclear necroptosis pathway resulting from ZMPSTE24 deficiency with pathogenic consequences in progeroid disorder and suggest RIPK1 as a feasible target for prelamin A-associated progeroid disorders.

Associations of global biomarkers of oxidative stress with osteoporosis, bone microstructure and bone turnover: Evidence from human and animal studies.

PURPOSE: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP_320, 360/420 nm for FlOP_360, and 400/475 nm for FlOP_400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats. METHODS: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure. RESULTS: In humans, higher levels of FlOP_320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP_360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP_400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP_320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm3; P = 0.001) than the control group. CONCLUSION: In conclusion, higher FlOP_320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation.

A subpopulation of luminal progenitors secretes pleiotrophin to promote angiogenesis and metastasis in inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a highly aggressive subtype of breast cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA sequencing, multiplex staining, and serum analysis in IBC patients, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for crosstalk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC.

The intestinal microbial metabolite acetyl l-carnitine improves gut inflammation and immune homeostasis via CADM2.

Intestinal symbiotic bacteria play a key role in the regulation of immune tolerance in inflammatory bowel disease (IBD) hosts. However, the bacterial strains directly involved in this regulation and their related metabolites are largely unknown. We sought to investigate the effects of intestinal microbial metabolites on intestinal epithelium and to elucidate their therapeutic potential in regulating intestinal mucosal inflammation and immune homeostasis. Here, we used metagenomic data from Crohn's disease (CD) patients to analyze the composition of intestinal flora and identify metabolite profiles associated with disease behavior, and used the mouse model of dextran sodium sulfate (DSS)-induced colitis to characterize the therapeutic effects of the flora metabolite acetyl l-carnitine (ALC) on DSS-induced colitis. We found that intraperitoneal injection of ALC treatment could significantly alleviate the symptoms of DSS-induced colitis in mice, including prevention of weight loss, reduction in disease activity index (DAI) scores, increasing of colonic length, reduction in histological scores, and improvement in intestinal barrier function. Further, transcriptome sequencing analysis and gene silencing experiments revealed that the absence of CADM2 abolished the inhibitory effect of ALC on the TLR-MyD88 pathway in colonic epithelial cells, thereby reducing the release of inflammatory factors in colon epithelial cells. And we confirmed a significant downregulation of CADM2 expression in intestinal tissues of CD patients compared to healthy people in a population cohort. In addition, we also found that ALC increased the ratio of Treg cells in colon, and decreased the ratio of Th17 cells and macrophages, thereby improving the immune tolerance of the organism. The proposed study could be a potential approach for the treatment of CD.

Acute retinal necrosis in a patient with cervical malignant tumor treated with sintilimab: a case report and literature review.

Acute retinal necrosis (ARN) is an inflammatory disease that is primarily caused by herpesvirus infection, most commonly varicella-zoster virus (VZV), followed by herpes simplex virus (HSV) and occasionally cytomegalovirus (CMV). Sintilimab is an immune checkpoint inhibitor (ICI) that can enhance the body's anti-tumor immune response. However, treatment with ICIs may lead to reactivation of the VZV. Here, we present a case of ARN caused by VZV infection in a patient receiving sintilimab for cervical cancer. A 64-year-old female patient developed vision loss and floaters with left eye redness for one week after 22 cycles of sintilimab for cervical cancer. Based on clinical manifestations, ophthalmological examination, and vitreous humor biopsy, the patient was diagnosed with acute retinal necrosis syndrome secondary to VZV. After receiving systemic antiviral and anti-inflammatory therapy, retinal necrosis lesions and visual function improved. In conclusion, clinicians should be aware of the risk of ARN when using sintilimab and should actively monitor patients for prompt diagnosis and optimal management of this rare adverse drug reaction.

An integrative pan-cancer bioinformatics analysis of MSRB1 and its association with tumor immune microenvironment, prognosis, and immunotherapy.

Methionine sulfoxide reductase B1 (MSRB1) is involved in the development and immune regulation of multiple tumors. However, the role of MSRB1 in the tumor microenvironment and its potential as a therapeutic target remain largely unknown. In this study, MSRB1 expression patterns were evaluated using pan-cancer RNA sequencing data from multiple cell lines, tissues, and single cells. The pan-cancer prognostic role of MSRB1 was assessed and the association between MSRB1 expression and certain cancer characteristics was analyzed. We showed that MSRB1 expression levels were increased in several types of cancer (P < 0.05) and in certain cell types (macrophages, dendritic cells, and malignant tumor cells). The upregulation of MSRB1 expression was due to DNA copy number amplification. Furthermore, MSRB1 was significantly associated with the activation of immune pathways (P < 0.05, NES > 0), immune cell infiltration, and expression of immune checkpoint molecules. In addition, high expression of MSRB1 was found in a series of in vivo and in vitro immunotherapy response models (P < 0.05), and showed resistance to most targeted drugs. Our results indicated that MSRB1 may regulate the tumor immune microenvironment through an immunoresponse and potentially influence cancer development. This could make it a promising predictive biomarker and therapeutic target for precise tumor immunotherapy.

Divergent Biosynthesis of Bridged Polycyclic Sesquiterpenoids by a Minimal Fungal Biosynthetic Gene Cluster.

The bridged polycyclic sesquiterpenoids derived from sativene, isosativene, and longifolene have unique structures, and many chemical synthesis approaches with at least 10 steps have been reported. However, their biosynthetic pathway remains undescribed. A minimal biosynthetic gene cluster (BGC), named bip, encoding a sesquiterpene cyclase (BipA) and a cytochrome P450 (BipB) is characterized to produce such complex sesquiterpenoids with multiple carbon skeletons based on enzymatic assays, heterologous expression, and precursor experiments. BipA is demonstrated as a versatile cyclase with (-)-sativene as the dominant product and (-)-isosativene and (-)-longifolene as minor ones. BipB is capable of hydroxylating different enantiomeric sesquiterpenes, such as (-)-longifolene and (+)-longifolene, at C-15 and C-14 in turn. The C-15- or both C-15- and C-14-hydroxylated products are then further oxidized by unclustered oxidases, resulting in a structurally diverse array of sesquiterpenoids. Bioinformatic analysis reveals the BipB homologues as a discrete clade of fungal sesquiterpene P450s. These findings elucidate the concise and divergent biosynthesis of such intricate bridged polycyclic sesquiterpenoids, offer valuable biocatalysts for biotransformation, and highlight the distinct biosynthetic strategy employed by nature compared to chemical synthesis.

4D Flow MRI of Portal Vein Hemodynamics in Healthy Volunteers and Patients with Chronic Liver Disease.

AIM: To identify age-matched healthy volunteers, non-cirrhotic chronic liver disease (CLD) and cirrhotic patients based on portal hemodynamic parameters using 4D flow MRI. METHODS: A total of 10 age-matched healthy volunteers and 69 CLD patients were enrolled and underwent 4D flow MRI prospectively. 4D flow MR images were processed by an MD in biomedical engineering working on the GTFlow platform. Portal hemodynamic parameters include net flow (mL/cycle), flow volume per second through the lumen (mL/sec), average flow velocity (cm/sec), and maximum flow velocity (cm/sec). The difference in portal hemodynamic parameters of 4D flow MRI was compared among healthy volunteers, non-cirrhotic CLD patients and patients with cirrhosis by one-way ANOVA or Kruskal-Wallis nonparametric test and post hoc tests. RESULTS: 10 CLD patients without cirrhosis and 56 patients with cirrhosis were eventually included, along with 10 healthy volunteers who were divided into three groups. 3 patients with cirrhosis whose image quality did not meet the requirements were excluded. There were no significant differences in portal hemodynamic parameters among the three groups except portal average velocity (P > 0.05). There was no statistical difference in all portal hemodynamic parameters of 4D flow MRI between healthy volunteers and patients with cirrhosis (P > 0.05). There were significant differences in portal average velocity between non-cirrhotic CLD patients, healthy volunteers and patients with cirrhosis, respectively (11.44±3.93 vs 8.10±2.66, P=0.013; 11.44±3.93 vs 8.60±2.22, P=0.007). CONCLUSION: Portal average velocity obtained by 4D flow MRI can be an auxiliary means to identify cirrhosis in patients with CLD.